Cancer Screening

Men's Health, Cancer Screening

PSA and free PSA (fPSA)Prostate cancer is a leading cause of cancer mortality. The American Cancer Society estimates that approximately 288,300 new cases will be diagnosed and 34,700 will die from prostate cancer in 2023 in the United States.7PSA, a serine protease, is produced by the epithelial cells of the prostate, and is produced by both benign and malignant cells. Abnormalities in the prostate gland architecture resulting from trauma or disease can lead to "leakage" of PSA into the bloodstream. Serum PSA exists primarily in either the free "non-complexed form" (fPSA) or in a "complex"(cPSA) primarily with the serum protease inhibitor, alpha 1-antichymotrypsin.8,9Typically, from 70 to 90 percent of the PSA in serum is cPSA, with the remainder being fPSA.10The %fPSA (ratio of fPSA to PSA) in serum has been demonstrated to significantly improve the discrimination of prostate cancer from benign prostatic conditions, especially in patients with PSA levels in the ≥4 to ≤10 ng/mL range. A higher %fPSA in serum is correlated with a lower probability of prostate cancer, while %fPSA values below 10 percent are more highly associated with cancer.10-12p2PSAProPSA and BPSA represent distinct forms of fPSA that demonstrate greater disease-association than PSA, fPSA, or cPSA alone.9Truncated forms of proPSA were found to be elevated in peripheral zone cancer tissue compared with BPH tissues.13The proPSA was elevated in prostate tumor tissue compared with BPH tissues.13The proPSA was elevated in prostate tumor tissue, while BPSA was elevated in nodular BPH transition zone tissue, compared to its concentration in peripheral zone tissue. ProPSA has been found as the native proPSA form containing a 7 amino acid pro leader peptide ([-7]proPSA),14as well as forms with truncated pro leader peptides. Truncated proPSA forms consist primarily of proPSA with a 5 amino acid pro leader peptide ([-5]proPSA), 4 amino acids ([-4]proPSA) and 2 amino acids (p2PSA).15,16The p2PSA has received the most attention since it was the primary form found in tumor extracts and shows higher immunostaining in prostate tumor than benign tissue.10,17Additionally, in vitro the most stable of the five identified proPSA forms is p2PSA.18,19Access Hybritech p2PSA was developed by Beckman Coulter, Inc. to measure p2PSA in serum. In studies of men with biopsy confirmed prostate cancer, p2PSA in the ≥4.0 to ≤10.0 ng/mL PSA range was shown to improve the specificity for cancer detection relative to %fPSA alone.10Reports from the literature are consistent with the intended use for the Access Hybritech p2PSA assay, used in conjunction with Access Hybritech PSA and fPSA assays to calculate the prostate health index (phi)in the further evaluation of patients with PSA levels in the ≥4.0 to ≤10.0 ng/mL range. Literature reports support the conclusion that precursor forms of PSA are emerging as potentially important diagnostic serum markers to augment PSA and improve prostate cancer detection.10,20-22Results of the Beckman Coulter, Inc. multi-center pivotal clinical trial found that Beckman Coulterphivalues significantly enhanced the clinical specificity relative to PSA and %fPSA for prostate cancer detection in the ≥4.0 ng/mL to ≤10.0 ng/mL PSA range.3At 95 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 14.1 percent compared to 9.9 percent for %fPSA. At 90 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 31.1 percent. At 80 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 46.1 percent. The improvement in clinical specificity for Beckman Coulterphirelative to %fPSA represents a substantial improvement in testing intended as an aid in distinguishing prostate cancer from benign prostatic conditions in men aged 50 years and older with total PSA ≥4.0 to ≤10.0 ng/mL, with digital rectal examination findings that are not suspicious for cancer.Beckman Coulterphiis anin vitroDiagnostic Multivariate Index Assay (IVDMIA), a combination of the results from the Access Hybritech PSA, free PSA and p2PSA assays designed to optimize clinical sensitivity and specificity as an aid in distinguishing prostate cancer from benign prostatic conditions. Beckman Coulterphiis used as an aid in distinguishing prostate cancer from benign prostatic conditions. A multi-center (seven clinical sites) clinical trial with a combination of prospective (97 percent) and retrospective (3 percent) subjects was conducted to test the effectiveness of Beckman Coulterphi. Subjects included men who were being evaluated to determine their prostate status.All subjects were between 50 and 84 years of age, with serum PSA values between 4 and 10 ng/mL (Hybritech calibration) and digital rectal examination (DRE) findings that were not suspicious for cancer. These men represent the "diagnostic gray zone," in which PSA has identified the men as high risk (25 percent cancer rate in men above 50 years of age), but where clinical specificity could be improved.23-25The study was blinded; clinicians did not have access to Beckman Coulterphivalues, and laboratory technicians did not have access to diagnoses. Inclusion criteria included subjects who signed informed consent, men ≥ 50 years of age, subjects who were untreated for prostate disease at the time of their blood draw, Hybritech PSA ≥4.0 and ≤10.0 ng/mL and ≤6 core biopsy. TRUS guided needle biopsy and diagnosis was histologically confirmed.Of the 658 total evaluable subjects, 652 (99.1 percent) had ≥8 core biopsies; 644 (97.9 percent) of the subjects had ≥10 core biopsies. Exclusion criteria included: prior history of prostate cancer, use of Avodart or Proscar at any time prior to blood draw, use of other drugs or therapies or recent prostatic manipulation that might have affected PSA values in the three months preceding the blood draw (including Propecia and androgen therapy including testosterone or Androgel), acute prostatitis, urinary tract infection, prior transurethral resection of the prostate (TURP), equivocal biopsy results, DRE with discrete nodules suspicious for cancer or PSA <4.0 or >10.0 ng/mL.A total of 658 men participated in the study (324 with prostate cancer and 334 without prostate cancer). Median age for both cancer and benign disease subjects was 63 years.Individual Patient Probability of Prostate Cancer on BiopsyBeckman Coulterphimay be used to determine the probability of prostate cancer on biopsy in individual men. Family and patient history can be used in combination with Beckman Coulterphiresults to determine the best individualized patient management decisions.In addition to the sensitivity and specificity analyses of the multi-site study data, we estimated an individual's probability of having detectable cancer based on the Beckman Coulterphivalues. In a population of men with PSA in the 4.0 to 10.0 ng/mL range and a non-suspicious DRE, a 25 percent positive biopsy rate has been previously reported.6,25The multi-site study population consisted of approximately 49.2 percent (324/658) cancer subjects and 50.8 percent (334/658) non-cancer subjects.Cancer probabilities based on the 49.2 percent proportion of cancer subjects would inflate the probability estimates for detecting cancer. Therefore, the proportion of cancer subjects was adjusted to 25 percent prior to calculating cancer probabilities for various Beckman Coulterphiscores. This adjustment provides accurate probabilities for the group of men in whom this test will be used. The bootstrap method was used to repetitively sample the multi-site study population.26Each sampling consisted of 334 (75 percent) benign subjects and 111 (25 percent) cancer subjects, for a total of 445 subjects. This random sampling process was repeated 1,000 times. We calculated mean cancer probabilities on biopsy and nonparametric 95 percent confidence intervals (2.5th and 97.5th percentiles). This repetitive sampling method increases the reliability of the probability of prostate cancer on biopsy estimates.Higher Beckman Coulterphivalues are associated with higher probability of prostate cancer.3Interpretation of Beckman CoulterphiBeckman Coulterphiis anin vitroDiagnostic Multivariate Index Assay (IVDMIA) used in combination with the Access Hybritech PSA, free PSA, and p2PSA assays designed to optimize specificity relative to %fPSA and PSA to determine the probability of prostate cancer on biopsy.3Beckman Coulterphihas been shown to significantly improve clinical specificity across the range of clinical sensitivity and cancer detection relative to PSA (p-value <0.001) and %fPSA (p-value = 0.009) in the PSA range of 4 to 10 ng/mL, in men ≥50 years of age with non-suspicious DRE.The selection of an appropriate Beckman Coulterphiscore that guides patient management considers the percentage of cancers detected (clinical sensitivity), and the percentage of men without cancer, in whom biopsy may be avoided (clinical specificity). For example, using the Hybritech calibration for PSA and free PSA, a Beckman Coulterphivalue of 22.1 corresponds to 95 percent sensitivity and 14.1 percent clinical specificity. Therefore, approximately one in seven men may avoid prostate biopsy while detecting 95 percent of cancers if their Beckman Coulterphivalue is less than 22.1.A Beckman Coulterphivalue of 27.0 corresponds to 90 percent clinical sensitivity and 31.1 percent clinical specificity. Therefore, nearly one in three men may avoid prostate biopsy while detecting 90 percent of cancers if their Beckman Coulterphivalue is less than 27.0.A Beckman Coulterphivalue of 31.3 corresponds to 80 percent clinical sensitivity and 46.1 percent clinical specificity. Therefore, approximately one in two men may avoid prostate biopsy while detecting 80 percent of cancers if their Beckman Coulterphivalue is less than 31.3. For men with a Beckman Coulterphivalue above the cutoff, the probability of prostate cancer on biopsy of cancer increases and may affect the clinical management of each patient.Low Beckman Coulterphiscores are associated with a lower probability of prostate cancer on biopsy, and higher scores are associated with an increased probability of prostate cancer on biopsy. The choice of an appropriate Beckman Coulterphiscore to be used in guiding clinical decision-making may vary for each patient and may depend in part on other clinically important factors or on family history of disease.

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Cancer Screening

CEA is a monomeric glycoprotein (molecular weight approximately 180,000 daltons) with a variable carbohydrate component of approximately 45% to 60%.1,2CEA, like AFP, belongs to the group of carcinofetal antigens produced during the embryonic and fetal period. CEA is mainly found in the fetal gastrointestinal tract and in fetal serum. It also occurs in slight quantities in intestinal, pancreatic, and hepatic tissues of healthy adults. The formation of CEA is repressed after birth and, accordingly, serum CEA values are hardly measurable in healthy adults.High CEA concentrations are frequently found in cases of colorectal adenocarcinoma.3,4Slight to moderate CEA elevations (rarely >10 ng/mL) occur in 20% to 50% of benign diseases of the intestine, pancreas, liver, and lungs (eg, liver cirrhosis, chronic hepatitis, pancreatitis, ulcerative colitis, Crohn's disease, emphysema).3,5Smokers also have elevated CEA values. The reactive epitopes of CEA have been characterized, and the available monoclonal antibodies classified, into six epitope groups.6-8The antibodies used in the Elecsys CEA assay react with epitopes two and five. The antibodies react with CEA and (as with almost all CEA methods) with the meconium antigen (NCA2).8Cross-reactivity with NCA1 is 0.7%.

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Cancer Screening, Women's Health

CA 27.29 is a highly polymorphic glycoprotein belonging to the mucin family and is the product of the muc-1 gene. It is most useful using serial measurements to monitor both the course of disease and response to therapy because the direct correlation of changing levels of CA 27.29 with clinical status. In patients with known metastases, a reduction in levels of this marker indicates a good response to treatment while increasing levels indicate resistance to therapy and progressive disease and justify further clinical evaluation and regular monitoring. It has also recently been shown that an elevation of CA 27.29 levels above the upper limit of normal in patients with no clinical evidence of disease is an early indicator of recurrence. An elevated serum CA 27.29 level in patients in remission of stage II or III breast cancer provided a positive predictive value of 83.3% for recurrent disease, with an average lead time of 5.3 months before recurrence was clinically established.

Cancer Screening, Digestive Health

This assay intended for the in vitro quantitative determination of CA 19-9 tumor-associated antigen in human serum and plasma.1The assay is indicated for the serial measurement of CA 19-9 to aid in the management of patients diagnosed with cancers of the exocrine pancreas. The test is useful as an aid in the monitoring of disease status in those patients having confirmed pancreatic cancer who have levels of CA 19-9 at some point in their disease process exceeding the median concentration determined for the apparently healthy cohort.The CA 19-9 values measured are defined by the use of the monoclonal antibody 1116-NS-19-9. The 1116-NS-19-9-reactive determinants on a glycolipid having a molecular weight of approximately 10,000 daltons are measured. This mucin corresponds to a hapten of Lewis-a blood group determinants and is a component of a number of mucous membrane cells.3,4Mucin occurs in fetal gastric, intestinal, and pancreatic epithelia. Low concentrations can also be found in adult tissue in the liver, lungs, and pancreas.2,5CA 19-9 assay values can assist in the differential diagnosis and monitoring of patients with pancreatic carcinoma (sensitivity 70% to 87%).6-12There is no correlation between tumor mass and the CA 19-9 assay values; however, patients with CA 19-9 serum levels >10,000 units/mL almost always have distal metastasis.2

Men's Health, Cancer Screening

In general, serum PSA levels increase due to physical changes to prostate architecture caused by trauma, infection, inflammation, prostate manipulation, benign prostatic hypertrophy (BPH), or malignancy.3,4The sensitivity of PSA levels to these changes serves as the basis for the clinical use of the test. The PSA concentration in the serum of healthy men is a millionfold lower than that in seminal fluid. PSA in seminal fluid is predominantly free or uncomplexed. In serum, the majority of PSA is bound to inhibitors, including α1-antichymotrypsin (ACT) and α2-macroglobulin (A2M). Measured total PSA consists of free and ACT-bound, since PSA complexed to A2M is not immunologically detectable.Catalona and coworkers found that one in four patients with normal DRE and PSA levels between 4.0 and 10.0 ng/mL have prostate cancer.2They recommend using a cutoff of 25% free PSA for this group of men (see Limitations) to identify individuals with an increased risk of prostate cancer. They found that 95% of men with cancer (as determined by biopsy) with normal DRE and total PSA between 4.0 and 10.0 ng/mL had percent free PSA of ≤25%. Their study further indicated that 20% of men with benign disease (as determined by biopsy) with normal DRE and a total PSA between 4.0 and 10.0 ng/mL had percent free PSA greater than the 25% cutoff.Alternatively, percent free PSA may be used to determine the relative risk of prostate cancer in individual men.2The following table lists the probability of prostate cancer for men with nonsuspicious DRE results and total PSA between 4.0 and 10.0 ng/mL, by patient age (see Limitations). See table.% Free PSA50 to 64 Years65 to 75 Years0.00−10.0056%55%10.01−15.0024%35%15.01−20.0017%23%20.01−25.0010%20%>255%9%

Cancer Screening

High concentrations of calcitonin occur not only in patients with malignant parafollicular or C-cell tumors (medullary thyroid carcinoma), but also in many patients with carcinomas of the lung; in some individuals with carcinoma of breast, carcinoids, islet cell tumors, apudomas, in patients with pancreatitis, thyroiditis and in renal failure. Hypergastrinemia may account for calcitonin elevations in the Zollinger-Ellison syndrome and in pernicious anemia. Medullary carcinoma arises from thyroid C cells (parafollicular cells). C-cell hyperplasia is a preneoplastic state in patients with MEN. Provocative tests that may be used for diagnosis of medullary thyroid carcinoma are pentagastrin and calcium infusion.3A combined calcium pentagastrin test is described in the see the online Endocrine Appendix: Calcium-Pentagastrin Stimulation.2,3These tests are much more useful than random plasma levels of calcitonin for the diagnosis of MCT. Early diagnosis of medullary carcinoma of thyroid is needed; total thyroidectomy is curative if the tumor is treated early. Medullary carcinomas of the thyroid gland have a variable histologic picture. Correlation between serum calcitonin levels and immunoperoxidase staining of the neoplastic thyroid tissue for calcitonin may assist in confirming the diagnosis in difficult cases. The direct manifestation of high calcitonin levels is secretory diarrhea in 30% of patients with medullary thyroid carcinoma.

Cancer Screening, Women's Health

Offered as part of multiple lab tests

Hormone Testing, Cancer Screening

Serotonin measurement is used in conjunction with urinary 5-hydroxyindoleacetic acid (5-HIAA) and/or serum chromogranin A in the diagnosis of carcinoid syndrome. Carcinoid tumors are slow-growing neuroendocrine tumors derived from enterochromaffin cells that are widely distributed throughout the body.1-4Approximately 65% of carcinoid tumors are found in the gastrointestinal tract from the foregut, midgut, and hindgut and another 25% originate in the bronchopulmonary tract.2,4About a quarter of cases present with distant metastases, half of which have unknown primary tumor location.2Carcinoid tumors secrete a variety of peptides and small molecules.1,4,5,6Midgut carcinoid tumors frequently produce serotonin. Serotonin-secreting carcinoids from other locations are less common. Serotonin (5-hydroxy-tryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin secretion in the gut causes an increase in gastrointestinal blood flow, motility, and fluid secretion. In healthy individuals, the great majority of serotonin made by the gut is converted by the liver and lungs to 5-hydroxy-indoleacetic acid (5-HIAA) via first pass metabolism prior to entering the general circulation.Serotonin secreting carcinoid tumors are relatively slow growing, and in most cases, asymptomatic.1,4,5The local, paracrine effect of increased serotonin on the gut intestine can cause diarrhea, malabsorption, and tumor mass producing discomfort.4,7Since most serotonin produced by carcinoid tumors is metabolized prior to reaching the circulation, the metabolic product, 5-HIAA in a 24-hour urine collection is usually the most important marker for diagnosing and monitoring treatment of the carcinoid syndrome.4,8The severity of carcinoid syndrome symptoms correlates with the level of 5-HIAA in urine. Urine 5-HIAA has been shown to have a sensitivity of 73% and specificity of 100% for diagnosing well-differentiated functional gastroenterohepatic neuroendocrine tumors.9Compared with patients having normal urinary 5-HIAA levels, patients with elevated levels, whether symptomatic or not, tend to have poorer prognosis.10-12In cases where a larger amount of serotonin reached the systemic circulation (advanced disease with liver metastases bypassing first pass metabolism), patients can present with a constellation of symptoms referred to as the carcinoid syndrome. The carcinoid syndrome can also occur in the absence of liver metastases in cases where tumor pathology causes direct venous drainage of serotonin bypassing first pass liver metabolism.6,13Carcinoid syndrome is relatively rare and is most commonly associated with midgut carcinoid tumors.3,4Carcinoid syndrome occurs in 20% of cases of well-differentiated endocrine tumors of the jejunum or ileum.6,13Carcinoid syndrome occurs less often with neuroendocrine tumors of other origins and is very rare in association with rectal neuroendocrine tumors.6,13Carcinoid syndrome is characterized by one or more symptoms, including diarrhea, dry flushing without sweating with or without palpitations, and intermittent abdominal pain.6Some patients also experience lacrimation and rhinorrhea.6,13Advanced or long-standing carcinoid syndrome can lead to carcinoid heart disease involving the tricuspid and pulmonary valves of the heart.7Significant elevations in urine 5-HIAA have been associated with carcinoid heart disease.14-16Other cardiovascular complications include bowel ischemia and hypertension.7Approximately one in five patients with carcinoid syndrome present with heart disease at diagnosis.6,13Carcinoid tumors are classified similarly, whether they produce symptoms of the carcinoid syndrome or not.17In healthy individuals, approximately 99% of dietary tryptophan is metabolized by the oxidative pathway into nicotinic acid (vitamin B3).4In carcinoid tumors, excessive conversion of tryptophan to serotonin can cause result in vitamin B3deficiency referred to as pellagra, a condition that is characterized by a triad of symptoms: diarrhea, dementia, and dermatitis.18

Cancer Screening, Men's Health

Elevated serum PSA concentrations have been reported in men with prostate cancer, benign prostatic hypertrophy, and inflammatory conditions of the prostate.

Cancer Screening, Digestive Health

Increased serum CEA levels have been detected in persons with primary colorectal cancer and in patients with other malignancies involving the gastrointestinal tract, breast, lung, ovarian, prostatic, liver and pancreatic cancers. Elevated serum CEA levels have also been detected in patients with nonmalignant disease, especially patients who are older or who are smokers. CEA levels are not useful in screening the general population for undetected cancers. However, CEA levels provide important information about patient prognosis, recurrence of tumors after surgical removal, and effectiveness of therapy.

Cancer Screening

Elevation of serum AFP above values found in healthy individuals occurs in several malignant diseases, most notably nonseminomatous testicular cancer and primary hepatocellular carcinoma. AFP is not recommended as a screening procedure to detect cancer in the general population.

Cancer Screening, Digestive Health

A large percentage of patients with gastrointestinal tumors (such as pancreatic, liver, gastric, colorectal tumors) and some other malignancies have been shown to have elevated serum CA 19-9 levels. Serum CA 19-9 levels may be useful for monitoring disease activity or predicting relapse following treatment. CA 19-9 should not be used as a screening test.

Cancer Screening, Women's Health

The CA 125 level can provide prognostic information in the follow-up management of patients with ovarian carcinoma. The assay should be used as an adjunctive test in the management of ovarian cancer patients. CA 125 is not recommended as a cancer screening procedure to detect cancer in the general population.

Cancer Screening, Women's Health

CA 15-3 may be useful for monitoring patients with metastatic breast cancer and certain ovarian cancers. The CA 15-3 values from sequential samples have a high correlation with the clinical course in most patients with metastatic breast cancer.

Cancer Screening, Digestive Health

The fecal occult blood test is an immunochromatographic fecal occult blood test that qualitatively detects human hemoglobin from blood in fecal samples. This is a useful screening aid for detecting primarily lower gastrointestinal (G.I.) disorders that may be related to iron deficiency anemia, diverticulitis, ulcerative colitis, polyps, adenomas, colorectal cancers or other G.I. lesions that can bleed. It is recommended for use by health professionals as part of routine physical examinations and in screening for colorectal cancer or other sources of lower G.I. bleeding.

Cancer Screening

A screening test for colorectal cancer, diverticulitis, colitis, polyps, and adenomas should be highly sensitive and highly specific for bleeding in the lower gastrointestinal tract, and should encourage patient compliance with obtaining a proper specimen. Guaiac-based tests for occult blood in stool suffer from a number of drawbacks, leading to a reduction in their sensitivity as well as production of false-positive results. These drawbacks include:• Detection of heme present in the stool, which can originate from bleeding anywhere in the gastrointestinal tract• Inability to distinguish human heme from heme present in many foods, such as dietary meats• Indiscriminate detection of peroxidase activity, which is present in a wide range of fruits and vegetables• Reaction with drugs and other substances that can cause false-negative resultsDetection of fecal occult blood by immunoassay eliminates the drawbacks seen with guaiac-based tests, and provides a sensitivity and specificity that is superior to guaiac. Immunochemical fecal occult blood tests utilize antihuman hemoglobin antibodies to detect the globin portion of undegraded human hemoglobin in stool. While hemoglobin from the upper gastrointestinal tract is mostly degraded by bacterial and digestive enzymes before reaching the large intestine, hemoglobin from lower gastrointestinal tract bleeding undergoes less degradation and remains immunochemically reactive. Thus, these tests are specific for lower gastrointestinal tract bleeding. Additionally, immunochemical fecal occult blood tests do not react with animal hemoglobin; peroxidase compounds; or with drugs, vitamins, or other substances that can produce false results, thereby eliminating the need for dietary or drug restrictions prior to patient specimen collection.The Polymedco OC-Auto Micro 80 immunochemical fecal occult blood test is capable of detection of as little as 100 ng of human hemoglobin per mL of feces, making it a much more sensitive assay than guaiac-based tests for detecting low levels of human fecal occult blood. It requires only one stool specimen collected from one bowel movement.

Cancer Screening

Immunofixation electrophoresis of serum or urine is most often ordered to evaluate a monoclonal globulin detected in a protein electrophoresis or to delineate a possible lymphoproliferative process, particularly myeloma. This procedure will characterize the specific light and heavy chain components of a monoclonal protein.

Cancer Screening, Men's Health

High concentrations of acid phosphatase are found in the prostate gland. Significant amounts are also found in platelets, bone, spleen, kidney and liver. Prostatic Acid Phosphatase (PAP) is a component of total acid phosphates and is a major constituent in seminal fluid and is also secreted in the urine. PAP is normally found in serum in very low levels.PAP measurement has found clinical application in the management of prostatic cancer patients. Serum PAP measurements have been useful in monitoring remission or relapse of a prostatic malignancy and in assessing the effectiveness of various treatment regimes. Thus, normalization in serum PAP levels has been observed following successful therapeutic intervention, while recurrent or residual disease has been associated with elevated levels of PAP.

Cancer Screening, Men's Health

In men over 50 years with total PSA between 4.0 and 10.0 ng/mL, the percent (%) free PSA gives an estimate of the probability of cancer. In these circumstances the measurement of the % free PSA may aid in avoiding unnecessary biopsies.Elevated levels of Prostate Specific Antigen (PSA) have been associated with benign and malignant prostatic disorders. Studies indicate that in men 50 years or older measurement of PSA is a useful addition to the digital rectal exam in the early detection of prostate cancer. In addition, PSA decreases to undetectable levels following complete resection of the tumor and may rise again with recurrent disease or persist with residual disease. Thus, PSA levels may be of assistance in the management of prostate cancer patients.

Cancer Screening

Diagnose myeloma, macroglobulinemia of Waldenström. Immunofixation is used to evaluate monoclonal gammopathy (M protein) found on serum protein electrophoresis; evaluate amyloidosis. Has application to the evaluation of lymphoproliferative disease (malignant lymphoma and others) and collagen disease in general. Of use in the diagnosis and characterization of immune deficient and dysgammaglobulinemic states.

Cancer Screening, Women's Health

CA 27.29 may be useful for monitoring patients for metastatic breast cancer.

Cancer Screening

Beta-2-microglobulin normally passes through the glomerulus into the proximal tubule where much of it is reabsorbed. Serum levels are therefore an index of glomerular function. When impaired, serum levels rise in inverse ratio to glomerular filtration rate. Increased amounts of beta-2-microglobulin are excreted in several renal disorders, e.g., Balkan nephropathy, heavy metal poisoning and renal tubular disease due to therapeutic agents. Serial levels of beta-2-microglobulin in serum and urine are used to evaluate transplant viability and anticipate rejection. Following a successful graft, serum levels decline toward normal. Increasing serum levels provide an early sign of rejection. Elevated levels are also noted in lymphproliferative disorders, neoplasms (malignant and benign), inflammatory disease, and autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's disease.

Cancer Screening

Calcitonin concentration is increased in patients with medullary thyroid carcinoma. Calcitonin concentrations may be used to monitor disease.

Cancer Screening

Thyroglobulin (Tg) is synthesized exclusively by thyroid follicular cells as the precursor protein for thyroid hormone biosynthesis.1,5,8Serum Tg reflects the integrated sum of Tg released into the blood stream and is related to three factors:1. Release of Tg into the blood stream is proportion to the mass of thyroid tissue present (from both normal and any tumor present).2. The effect of any thyroid injury caused by inflammation associated with thyroiditis; radioactive iodine (RAI) therapy; fine needle aspiration (FNA) biopsy; or surgery.3. The degree of TSH-receptor stimulation from endogenous TSH, recombinant human TSH (rhTSH), human chorionic gonadotropin (during pregnancy) or antibodies that stimulate the TSH receptor (Graves' disease).Measurement of serum Tg is used primarily in the postoperative management and long-term surveillance of patients with DTC. Serum Tg concentrations reflect the residual mass of thyroid tissue present (normal remnant and/or tumor) and the effect of the three factors listed above.1,5,7Since Tg production is thyroid-specific but not tumor-specific, patient-related factors influence the interpretation of serum Tg concentrations. Postoperative serum Tg levels are related to the amount of residual normal and tumor tissue, recent thyroid injury, and the TSH status of the patient. In patients who have not had a total thyroidectomy and radioiodine remnant ablation, the interpretation of serum Tg measurements is limited by the inability to differentiate between tumor and thyroid remnant, though trends over time can be informative. An increase in serum Tg levels over time while on suppressive thyroxine therapy is highly suggestive of tumor recurrence or progression.7Thyroglobulin antibody (TgAb) is detected in approximately 10% of the general population and in 20% of patients with DTC.5,9,10Several studies have suggested that the quantitative TgAb concentrations can serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.11Guidelines recommend that TgAb be measured in all specimens that are tested for Tg because TgAb interference with Tg-IMA measurements is associated with underestimation of Tg and the potential for reporting inappropriately low or undetectable values that can disguise the presence of disease.1,7,8,12-15Historically, there have been no reliable methods for the accurate measurement of Tg in patients with TgAb; however, new assays employing trypsin digestion of serum proteins followed by LC-MS/MS quantitation of Tg-specific tryptic peptides allow for the accurate quantitation of Tg in the presence of TgAb.6Reference ranges established by testing normal, euthyroid subjects have little relevance when interpreting serum Tg concentrations in differentiated thyroid cancer (DTC) patients after thyroidectomy. Current guidelines recommend using a given assay's functional sensitivity (or LOQ) as the clinical threshold for distinguishing biochemically negative patients from those with residual Tg-producing tissue.8• The Beckman Coulter IMA Tg assay (used for TgAb-negative samples) has a functional sensitivity/limit of quantitation (LOQ) of 0.1 ng/mL.• The LC/MS-MS Tg assay (used for TgAb-positive patients) has a functional sensitivity/limit of quantitation (LOQ) of 0.2 ng/mL.For the detection of interfering TgAb, the lower limit of detection (LOD) of the TgAb assay should be used. TgAb interference with Tg-IMA assays can occur at low levels of TgAb.• The Beckman Coulter TgAb assay has a limit of detection (LOD) of 0.9 IU/mL.

Cancer Screening

Thyroglobulin (TG) is a secretory product only of the thyroid gland. The major clinical use of serum TG measurement is to monitor, but not to diagnose, patients with well-differentiated thyroid cancers. The measurement of thyroglobulin, after thyroidectomy and ablation of the thyroid gland, is useful to determine metastasis.Deficient TG synthesis is observed in infants with goitrous hypo-thyroidism. Most patients with thyroid autoimmune disease have thyroglobulin antibody. With immunometric assays (sandwich assays), TGAB interference typically produces inappropriately low TG results, most likely caused by endogenous TG immune complexes that block one or more of the reagent antibodies from binding endogenous TG.

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Cancer Screening

Thyroglobulin (Tg) is synthesized exclusively by thyroid follicular cells as the precursor protein for thyroid hormone biosynthesis.1,4,5The serum Tg reflects the integrated sum of Tg released into the blood stream and is related to three factors:1. Release of Tg into the blood stream is proportion to the mass of thyroid tissue present (from both normal and any tumor present).2. The effect of any thyroid injury caused by inflammation associated with thyroiditis; radioactive iodine (RAI) therapy; fine needle aspiration (FNA) biopsy; or surgery.3. The degree of TSH-receptor stimulation from endogenous TSH, recombinant human TSH (rhTSH), human chorionic gonadotropin (during pregnancy) or antibodies that stimulate the TSH receptor (Graves' disease).Measurement of serum Tg is used primarily in the postoperative management and long-term surveillance of patients with DTC. Serum Tg concentrations reflect the residual mass of thyroid tissue present (normal remnant and/or tumor) and the effect of the three factors listed above.1,4Since Tg production is thyroid-specific but not tumor-specific, patient-related factors influence the interpretation of serum Tg concentrations. Postoperative serum Tg levels are related to the amount of residual normal and tumor tissue, recent thyroid injury, and the TSH status of the patient.It should be noted that the thyroid tumors of some patients fail to secrete a detectable Tg concentration or may secrete abnormal Tg isoforms that are not detected by some assays used to measure Tg. Measurement of preoperative Tg levels can provide the clinician with insights regarding the tumor's Tg production and secretion and support the utility of postoperative Tg monitoring.Thyroglobulin antibody (TgAb) is detected in approximately 10% of the general population and in 20% of patients with DTC.4,6-8Several studies have suggested that the quantitative TgAb concentrations can serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.9Guidelines recommend that TgAb be measured in all specimens that are tested for Tg because TgAb positivity is associated with discordance in thyroglobulin values measured by radioimmunoassay (RIA) compared to values produced by immunometric assays (IMA) for Tg.10TgAb interference with Tg-IMA measurements is associated with underestimation of Tg and the potential for reporting inappropriately low or undetectable values that can disguise the presence of disease.5,10-12Several lines of evidence suggest that the higher values of Tg assayed by RIA in the presence of TgAb may be more physiologically appropriate than the lower Tg values produced by ICMA methods. Patients with Graves' hyperthyroidism and TgAb often have unexpectedly low or undetectable IMA-Tg levels with RIA-Tg values are high and decrease in response to therapy.4,13,14Also TgAb-positive euthyroid individuals often have RIA-Tg within the range established for RIA-Tg in TgAb-negative euthyroid individuals. In contrast, IMAs produce low or undetectable Tg levels for many of the same individuals.10Although RIA-Tg methods tend to be more resistant to TgAb interference than IMA-Tg methods, no immunoassay methodology for measurement of Tg is completely free from the potential for TgAb interference.15Reference ranges established by testing normal, euthyroid subjects have little relevance when interpreting serum Tg concentrations in differentiated thyroid cancer (DTC) patients after thyroidectomy. Current guidelines recommend using a given assay's functional sensitivity (or LOQ) as the clinical threshold for distinguishing biochemically negative patients from those with residual Tg-producing tissue.5• Beckman Coulter Tg IMA functional sensitivity (LQQ): 0.1 ng/mL• Endocrine Sciences Radioimmunoassay for TgAb positive patients, functional sensitivity (RIA-Tg): 2.0 ng/mLFor the detection of interfering TgAb, the lower limit of detection (LOD) of the TgAb assay should be used. Even as low levels of TgAb, there may be interference with Tg-IMA assays.• Beckman Coulter TgAb limit of detection (LOD): 0.9 IU/mL

Cancer Screening

Neuron-specific enolase (NSE) is an enzyme that is found in the cytoplasm of neurons and neuroendocrine cells.2,3The production of NSE occurs late in neural differentiation, thus making NSE an index of neural maturation.2Increased serum levels of NSE may occur in patients with of neuroendocrine tumors (NETs).2,4-13A number of NETs are considered to be “nonfunctioning” in that they do not produce elevated serum concentrations of substances that cause endocrine symptoms. NSE is similar to chromogranin A (CgA) in that it can serve as a general neuroendocrine tumor marker that can be of clinical value in in the assessment of non-functioning tumors.4,14NSE can be particularly useful in the assessment of patients with high-grade, poorly differentiated tumors.4,14Serum NSE levels are often elevated in patients with small-cell lung cancer (SCLC) and NSE levels are applied as a biomarker for disease staging and monitoring.3,11,13-27NSE levels have been shown to correlate with tumor burden, number of metastatic sites and response to treatment in SCLC.6,28,29A meta-analysis of 11 studies determined that SCLC patients with higher levels of NSE had a poorer prognosis than those with lower levels of NSE.30Increased levels of NSE have been also reported in non-small cell lung cancer (NSCLC).2,31,32Differentiation between SCLC and NSCLC can have prognostic and therapeutic value, due to the dissimilar behavior of these malignancies.2,33In a comparative analysis of the performance of several NSE assays, Stern and coworkers found that the Brahms Kryptor assay had a 22% sensitivityfor distinguishing cancer patients (SCLC and NSCLS) from benign lung disease with a specificity of 95% using a cut-off concentration of 20 ug/L.34In the same study, the Brahms assay had a 55% sensitivity for distinguishing SCLC form NSCLS at 95% specificity,34employing an NSE cut-off of 21ug/L. This was the highest sensitivity of the seven NSE methods evaluated.Raised serum levels of NSE have been found in patients with neuroblastoma, especially in widespread and metastatic disease, with high serum levels correlated with significantly worse outcome in terms of disease-free survival.35-37Increased serum NSE levels have also been observed in patients with diverse conditions including: melanoma, seminoma, renal cell carcinoma, Merkel cell tumor, carcinoid tumors, dysgerminomas and immature teratomas, malignant pheochromocytoma, Guillain-Barrésyndrome and Creutzfeldt-Jakob disease.2Measurement of serum NSE has been applied to the assessment of neuronal injury37and the estimation of brain damage in conditions including: ischemic stroke,38intracerebral hemorrhage,39,40seizure,41after cardiopulmonary resuscitation for cardiac arrest42and in traumatic brain injury.43

Cancer Screening

Quantitative determination of NSE in serum may be valuable in the management of patients with suspected or diagnosed SCLC or neuroblastoma, to monitor the effect of treatment, to aid in the detection of recurrent disease, and to evaluate prognosis in patients.

Cancer Screening, Men's Health

For post-prostatectomy patients.The lower limit of accurate quantification for this assay is 0.02 ng/mL. PSA values less than 0.02 ng/mL cannot be accurately measured and will be reported as less than 0.02 ng/mL. Specimens with PSA levels below the lower limit of accurate quantification should be considered as negative. In patients with a negative result for post-prostatectomy PSA, serial monitoring of PSA levels at regular intervals, along with physical examinations and other tests, may help to detect recurrent prostate cancer.

Cancer Screening, Men's Health

Offered as part of multiple lab tests

Cancer Screening

Monoclonal increases in IgG or IgA are often associated with diseases such as multiple myeloma, lymphomas or leukemia. A monoclonal increase in IgM is commonly associated with Waldenström's macroglobulinemia.

Cancer Screening

Vascular endothelial growth factor (VEGF) is a homodimeric 34 to 45 kilodalton, heparin-binding glycoprotein. VEGF has potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells.1,2VEGF expression is regulated by hypoxia, with levels increasing when cells detect an environment low in oxygen. Physiologically, VEGF induces new blood vessel formation during embryonic development, after tissue injury and in response to blocked vessels. VEGF is thought to play an important role in several physiologic processes, including wound healing, ovulation, menstruation, maintenance of blood pressure and pregnancy.1VEGF has also been associated with a number of pathologic processes that involve angiogenesis, including arthritis, psoriasis, macular degeneration and diabetic retinopathy.1,3POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted.4The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. Elevated VEGF is highly specific for POEMS syndrome (though not pathognomonic) and thought to be involved in the pathophysiology of systemic features including organomegaly and volume overload. VEGF levels reflect disease activity, falling with treatment and rising with disease progression or relapse. Monitoring VEGF levels may be useful as a disease prognostic marker.5In general, the growth and spread of tumors has been shown to be dependent on the development of increased vascularization in the tumor vicinity in order to maintain sufficient oxygenation.1,6Tumor expression of proangiogenic factors, including VEGF, has been associated with advanced tumor progression in a number of human cancers.7,8Increased expression of VEGF has been associated with poorer prognosis in patients with cancer of the colon,9-11stomach,12-14pancreas,15,16breast,17-20ovary,21,22prostate,23,24liver,25oral squamous cell,26bone27and in melanoma.28Serum VEGF levels are significantly higher than plasma levels. This is thought to reflect the fact that VEGF is released into the serum from platelets as part of the clotting process.29It has been hypothesized that VEGF released from activated platelets may have a role in angiogenesis during wound healing and may also be associated with pathological conditions, such as atherosclerosis, tumor growth and metastasis formation.29In different studies, serum VEGF12,21,22,25,26and plasma VEGF11,17,23,24levels have been found to correlate with the clinical status of patients with cancer.

Autoimmune & Inflammation, Cancer Screening

To evaluate the level of IL-6 in serum samples.

Cancer Screening

This assay is intended for research use only. It may have value in the evaluation of patients with various types of cancer who are being considered for anti-angiogenesis therapy.

Autoimmune & Inflammation, Cancer Screening

Test is for research use only, and is for use in patients previously diagnosed with T-cell lymphoma.

Cancer Screening

Low numbers of NK cells are found in individuals who are susceptible to viral infections, including cytomegalovirus and varicella.

Cancer Screening, Women's Health

Estrogen and progesterone receptor assays are routinely performed on breast carcinomas to assess responsiveness to endocrine therapy and prognosis. HER-2 is associated with cellular proliferation activity. Over-expression is observed in 20-25% of women with breast cancer. These patients are potential candidates for monoclonal therapy.

Cancer Screening, Women's Health

Estrogen and progesterone receptor assays are routinely performed on breast carcinomas to assess responsiveness to endocrine therapy and prognosis.

Cancer Screening

Chromogranin-A (CgA) is an acidic glycoprotein expressed in the secretory granules of most normal and neoplastic neuroendocrine (NE) cell types, where it is released together with peptide hormones and biogenic amines. Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they synthesize, store, and secrete peptides, e.g., CgA and amines. CgA is secreted from neuroendocrine-derived tumors including foregut, midgut and hindgut gastrointestinal NETs, pheochromocytomas, neuroblastomas, medullary thyroid carcinomas, some pituitary tumors, functioning and non-functioning pancreatic NETs.Significantly elevated CgA levels have been found in patients with other diseases, such as impaired renal function, untreated benign essential hypertension, gastritis, prostatic carcinoma, and hyperparathyroidism. The best-characterized circulating biomarker that identifies NETs in general is CgA. Monitoring blood CgA levels may effectively provide information that is helpful in delineating tumor burden and rate of tumor growth, predicting tumor response to therapy and providing some indication as to prognosis.

Cancer Screening

Chromogranin A1is a hydrophilic glycoprotein that is stored in the chromaffin granules of the neuroendocrine cells.2The physiologic role of CgA has not been fully elucidated, but studies suggest that it serves as a precursor to other biologically active peptides and facilitates the production of other hormones and neuropeptides.2-4In healthy individuals, most of the CgA found in the circulation is derived from enterocromaffin- like (ECL) cells5found in the gastric glands of the stomach in the vicinity of parietal cells. ECL cells serve to stimulate the production of gastric acid via the neuroendocrine release of histamine.5Neuroendocrine cells receive neuronal input that stimulates them to release a variety of molecules (in many cases including CgA). Neuroendocrine cells are ubiquitous throughout the body and can be found in numerous organs including the gastrointestinal (GI) tract (in the small intestine, rectum, stomach, colon, esophagus and appendix), the gallbladder, the pancreas (islet cells) and the thyroid (C cells). Neuroendocrine cells are also found in the lungs and airways into the lungs (bronchi), as well as the respiratory tract of the head and neck. The pituitary gland, the parathyroid glands and the inner layer of the adrenal gland (adrenal medulla) are largely made up of neuroendocrine cells. Other locations of neuroendocrine cells include the thymus, kidneys, liver, prostate, skin, cervix, ovaries and testicles.Neuroendocrine neoplasms (NENs) can originate from any of the neuroendocrine cells that are scattered throughout the body. Because many NENs are secretory, the measurement of circulating biomarkers can be helpful for their diagnosis as well as for estimating tumor burden, assessing tumor response to treatment, monitoring disease progression, and predicting outcomes.5-19Patients with well-differentiated NENs frequently express elevated blood levels of CgA. Numerous studies have documented the utility of measuring circulating CgA levels in patients with a variety of NENs, including carcinoids,21tumors of the gastroenteropancreatic tract,5,15,20,24-26pheochromocytomas,22,23neuroblastomas,27islet cell tumors,16,28and other amine precursor uptake and decarboxylation (APUD) tumors.15,29,30CGA can be elevated in patients with multiple endocrine neoplasia, type 1 (MEN1) and is used for the routine surveillance of this condition.31,32Prostate cancers often contain cells with partial neuroendocrine differentiation. The value of CgA as a biomarker of prostate cancer has been extensively evaluated with several studies suggesting that it has prognostic utility in certain cases, such as in combination with NSE assessment or in patients treated with certain specific therapies.33-36

Blood Disorders, Cancer Screening

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) recommend the use of serum free light chain assays in the initial diagnostic work-up of multiple myeloma and related disorders."Use of free light chain (FLC) assay along with SPEP and SIFE yields high sensitivity while screening for MM and related plasma cell disorders. Therefore, this assay is now included as a part of the initial diagnostic work-up in the NCCN Multiple Myeloma Guidelines."1If screening for plasma cell dyscrasias, the International Myeloma Working Group recommends a screening panel consisting of serum free light chain assay, serum protein electrophoresis (SPEP), and serum immunofixation (IFE) to maximize sensitivity. (A 24-hour urine IFE can be added if AL amyloidosis is suspected.)2

Hormone Testing, Cancer Screening

Offered as part of multiple lab tests

Hormone Testing, Cancer Screening

Offered as part of multiple lab tests

Cancer Screening

Transforming Growth Factor (TGF) plays a crucial role in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Transforming growth factor beta is found in hematopoietic (blood-forming) tissue and initiates a signaling pathway that suppresses the early development of cancer cells. It enhances the deposition of extracellular matrix and may play potential role in wound healing and cirrhosis formation. Many cells synthesize TGF-b and almost all of them have specific receptors for this peptide.

Cancer Screening

Useful in the evaluation of pheochromocytoma.

Cancer Screening

N-type calcium channel antibodies are more highly associated with primary lung cancer than P/Q-type. One or all of the autoantibodies in the myasthenia gravis (MG)/LEMS evaluation can occur with neoplasia without evidence of neurological impairment. One or both calcium channel antibodies (P/Q and N) can occur with paraneoplastic and idiopathic cerebellar ataxia, encephalomyeloneuropathies, and autonomic neuropathy. Classical symptoms of LEMS include proximal muscle weakness, fatigability, dry mouth and impotence. When presentation is further complicated with oculobulbar weakness, these symptoms can easily be misinterpreted as MG. However, because VGCC antibodies are positive in only approximately 5% of MG patients, the measurement of these antibodies is very useful in distinguishing LEMS from MG.

Cancer Screening, Heart Health & Cardiovascular

Vascular endothelial growth factor (VEGF) is a homodimeric 34 to 45 kilodalton, heparin-binding glycoprotein. VEGF has potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells.1,2VEGF expression is regulated by hypoxia, with levels increasing when cells detect an environment low in oxygen. Physiologically, VEGF induces new blood vessel formation during embryonic development, after tissue injury and in response to blocked vessels. VEGF is thought to play an important role in several physiologic processes, including wound healing, ovulation, menstruation, maintenance of blood pressure and pregnancy.1VEGF has also been associated with a number of pathologic processes that involve angiogenesis, including arthritis, psoriasis, macular degeneration and diabetic retinopathy.1,3POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted.4The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. Elevated VEGF is highly specific for POEMS syndrome (though not pathognomonic) and thought to be involved in the pathophysiology of systemic features including organomegaly and volume overload. VEGF levels reflect disease activity, falling with treatment and rising with disease progression or relapse. Monitoring VEGF levels may be useful as a disease prognostic marker.5In general, the growth and spread of tumors has been shown to be dependent on the development of increased vascularization in the tumor vicinity in order to maintain sufficient oxygenation.1,6Tumor expression of proangiogenic factors, including VEGF, has been associated with advanced tumor progression in a number of human cancers.7,8Increased expression of VEGF has been associated with poorer prognosis in patients with cancer of the colon,9-11stomach,12-14pancreas,15,16breast,17-20ovary,21,22prostate,23,24liver,25oral squamous cell,26bone27and in melanoma.28Serum VEGF levels are significantly higher than plasma levels. This is thought to reflect the fact that VEGF is released into the serum from platelets as part of the clotting process.29It has been hypothesized that VEGF released from activated platelets may have a role in angiogenesis during wound healing and may also be associated with pathological conditions, such as atherosclerosis, tumor growth and metastasis formation.29In different studies, serum VEGF12,21,22,25,26and plasma VEGF11,17,23,24levels have been found to correlate with the clinical status of patients with cancer.

Cancer Screening

HTLV-I/II DNA PCR is a highly specific and sensitive method used to detect HTLV-I/II proviral DNA in clinical specimens. In addition, the assay can also differentiate between HTLV-I and HTLV-II infected individuals.

Cancer Screening

Normetanephrine (NM) and metanephrine (MN) are the extra-neuronal catechol-o-methyl transferase (COMT) metabolites of the catecholamines norepinephrine and epinephrine, respectively. Measurement of plasma metanephrines is more sensitive (but may be less specific) than measurement of catecholamines for the detection of heochromocytoma. Proper interpretation of results requires awareness of recent medication/drug history (e.g., antihypertensive agents, alcohol, cocaine) and other pre-analytical factors (e.g., stress, severe congestive heart failure, myocardial infarction) that influence release of catecholamines and metanephrines.

Autoimmune & Inflammation, Cancer Screening

Interleukin-2 (IL‑2) stimulates an immune response on target cells via a high affinity receptor (IL-2R) composed of alpha, beta and gamma subunits.5,6The alpha subunit (also referred to as CD25) has no signaling capacity but confers on the receptor the ability to bind IL-2 with high-affinity.6Signals from this receptor activate transcription factors that promote cell survival and proliferation, the two principal actions of IL-2.6Upon antigen stimulation, T cells both produce and respond to IL-2, leading to the preferential expansion of antigen-specific clones. IL-2R is also expressed on regulatory T cells (Tregs), cells that are essential for maintaining self-tolerance, and their depletion results in autoimmunity.6A soluble form of the IL-2R alpha subunit (sIL-2Rα) is released into the serum from the membranes of activated lymphocytes after shedding by proteolytic cleavage.7Release of sIL-2Rα is proportional to the cell surface expression of IL-2R.8sIL-2Rα is detected in the serum of healthy individuals and increases in association with various types of inflammation or neoplasms.5,9-11Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome of excessive immune system activation driven mainly by high levels of interferon gamma.2HLH is induced by aberrantly activated macrophages and cytotoxic T cells.12The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults.12Guidelines for the diagnosis and prognostication of HLH include the measurement sIL-2Rα.13-17Since T-cell activation is central to HLH pathogenesis, elevated sIL-2Rα is almost always observed in untreated HLH.18-20Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory or autoimmune disorders, in which case it is called macrophage activation syndrome.12,21Patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome.12It has been suggested that sIL-2Rα can be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions.22Since T-cell activation is a hallmark of granuloma formation, diseases with extensive granulomatous lesions often present with elevated sIL-2Rα levels. sIL-2Rα has been reported to be an effective marker for measuring disease in patients with tuberculosis, sarcoidosis eosinophilic granulomatosis with polyangiitis and common variable immunodeficiency.4,23-28Elevated levels have been reported in T-cell mediated diseases including multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis.29-33Increased sIL-2Rα have also been reported in classical autoantibody mediated diseases including myasthenia gravis and pemphigus.34,35Serum sIL-2Rα levels have been found to be elevated in most types of hematolymphoid neoplasms, including Hodgkin's lymphomas, non‑Hodgkin lymphomas, acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, and others.1The highest levels of sIL-2Rα have been reported in adult T‑cell lymphoma/leukemia36and hairy cell leukemia.37Elevated levels have been reported in follicular and diffuse large B-cell lymphoma.5,38-43An extremely elevated sIL-2Rα (>10- to 20-fold above normal) in a non-infantile patient suggests undiagnosed lymphoma, especially when ferritin is not similarly elevated.44,45An association between increased levels of sIL-2Rα and poor outcome has also been reported in several non-lymphoid cancers.1,33,46

Cancer Screening

Methylated Septin 9 is a DNA marker associated with colorectal cancer.

Cancer Screening, Blood Disorders

Offered as part of multiple lab tests