Marker 72-4
Kiliano Ratha
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Among the new tumor markers that have been recently proposed, CA 72-4 is of particular interest, not only for its capabilities in diagnosing and monitoring certain neoplastic diseases, but also for its excellent specificity. Several studies focused on the potential clinical usefulness of CA 72-4 in gastrointestinal (GI) and gynecological cancer, showing a sensitivity of approximately 40% in colorectal and gastric cancer and 50% in ovarian cancer, with an overall specificity of more than 95%. Longitudinal evaluations of patients with either GI or gynecological malignant diseases demonstrated that significant elevations of CA 72-4 serum levels may be predictive of recurrent disease. Moreover, the combination of CA 72-4 with other known serum markers, such as CEA and CA 19-9 for GI cancer or CA 125 for ovarian cancer, indicated that an increase in the sensitivity can be achieved without substantial changes in the overall specificity, improving the possibility of monitoring these patients. In conclusion, these results provide a strong argument for the use of CA 72-4 in the management of these neoplastic diseases.
About a month ago, my wife had a panel of serum tumor markers tested in Europe. The reason why she did it is to serve as a "negative" control for her mother (who is currently a 3-year cancer survivor). However, we unexpectedly found that my wife's CA72-4 level was elevated to 24 and to 16U/ml (analysis done in different labs on consecutive days). The normal upper limit is 6.9U/ml. Her other markers (CEA, CA19-9, CA125, CA15-3, HE4 and AFP) were normal. Upon our return home to the USA, she had several tests (including abdominal/pelvic CT), which so far did not reveal the specific reason for this elevation. As with all tumor markers, the most important thing is to follow the dynamics of CA72-4. And here we have a big problem: although CA72-4 is a commonly tested marker in Europe and many other countries, it is not FDA-approved in the USA. Therefore, we would be enormously grateful if someone would let us know whether it is possible to measure it here. We would also appreciate hearing from anyone who had an elevated CA72-4 level and how everything developed.
And which I find interesting in the attached PDF where is says at the bottom "Not for distribution in the USA"? : -diagnostics.ch/content/dam/corporate/roche-dia_ch/documents/broschueren/professional_diagnostics/serumarbeitsplatz/immunologie/tumor-marker/EN_CA72-4_FactSheet.pdf
I would suggest you give this company a call. It looks as if you can purchase the test yourself. You should be able to have the blood drawn at a local lab, like Quest. The lab can prepare the sample and either you or the lab can ship it. I have shipped blood samples before. It's not hard. You just have to follow the instructions.
Many thanks for your suggestions (the Roche test is actually the one that we used in Europe). We did contact Dr. Hindenburg (senior author of the paper that you mentioned), but he is no longer testing for CA72-4. We have now written to the company that supplied the reagents that he used to see if they are working with any other clinicians.
thank you for your concern - and for your suggestions. My understanding is that the product that you mentioned is a semi-purified form of CA72-4 to be used as a standard/control for assays. However, I will contact the company to see if they know of diagnostic labs that can test for CA72-4. I'll also contact Quest directly.
Elevated CA 72-4 levels in serum and plasma have been reported in various malignant diseases including carcinomas of pancreas, stomach, gallbladder, colon, ovaries, cervix and endometrium. The highest diagnostic sensitivities, according to current studies, are found for carcinomas of the gastrointestinal tract and ovaries.
Although some benign diseases such as rheumatic diseases or ovary cysts may also result in elevated levels of CA 72-4, clinical studies demonstrated diagnostic specificity of more than 95% for gastrointestinal and ovarian malignancies. There is a good correlation between CA 72-4 levels and tumor stage and size.
CA 72-4 is the marker of choice for the therapeutic monitoring and follow-up care of gastrointestinal cancer patients. Suitable second markers are CA 19-9 or CEA. It has been used as an independent marker for the therapeutic monitoring and follow-up care of ovarian cancer patients, in particular in CA 125 negative patients.
The MUC1 gene encodes for a high molecular weight glycoprotein found in specific tissues throughout the body. The product of the MUC1 gene has many varieties of carbohydrate chains and one of them is cancer (or carbohydrate) antigen 72-4 (CA 72-4), which is found in the bloodstream in certain types of cancers. CA 72-4 is elevated in gastrointestinal cancers and ovarian cancers. Measurement and evaluation of CA 72-4 levels are done in combination with other cancer markers. CA 72-4 measurement is not useful for detecting oligometastases of colorectal cancer but is positive in advanced metastatic tumors. Its utility as a predictor of survival in gastric cancer is being investigated.
The CA 72-4 measurements can be used in combination with other cancer markers to detect gastric cancer. CA 72-4 is a specific marker (100%) for esophageal, stomach, and colon cancer, but is not very sensitive (18%, 32%, and 56%, respectively) when used alone. When used in combination with other cancer markers, there is an increased sensitivity for gastric cancer to 81% and an increased sensitivity for esophageal cancer to 74%. The measurement of CA 72-4 can be used in conjunction with CA 125 for ovarian cancer while is also increased in endometrial cancer. CA 72-4 is increased in 85% of cases of invasive breast carcinoma.
Laboratory test results are the most important parameter for the diagnosis and monitoring of all pathological conditions. 70%-80% of diagnostic decisions are based on laboratory tests. The correct interpretation of laboratory results allows a doctor to distinguish "healthy" from "diseased".
Laboratory test results should not be interpreted from the numerical result of a single analysis. Test results should be interpreted in relation to each individual case and family history, clinical findings, and the results of other laboratory tests and information. Your personal physician should explain the importance of your test results.
Tumor-associated glycoprotein 72 (TAG-72) is a glycoprotein found on the surface of many cancer cells, including ovary,[1][2][3] breast, colon,[4] lung, and pancreatic cancers.[5][6] It is a mucin-like molecule with a molar mass of over 1000 kDa.[7]
TAG-72 is a tumor marker measured with radioimmunoassays like CA 72-4, which uses the monoclonal antibodies indium (111In) satumomab pendetide and iodine (125I) minretumomab.[8][9][10][11][12] This assay has a good specificity for gastric cancer, with a correlation to the neoplasia's extension. It is used to identify relapses of the disease and to follow up the treatment.
Tumor biomarkers play a crucial role in monitoring of response to therapy and in post-treatment surveillance of various gastrointestinal and gynecological malignancies. While the clinical value of FDA-approved tumor markers such as CEA, CA19-9 and CA125 has been established, adequate data to support FDA approval of CA72-4 as a potential biomarker are lacking and its measurement is only considered experimental and investigational.
CA72-4. The tumor marker CA72-4 was first described by Dr. Jeffrey Schlom in the early 1980s as a novel antigen reactive to murine antibodies produced by mice that were immunized with membrane-enriched fractions of human metastatic mammary carcinoma cells. Several antibodies were identified to have preferential binding to human carcinoma cells with sparing of normal adult tissues.
Despite early studies indicating a possible role of CA72-4 in the monitoring of advanced disease, testing for CA72-4 has not been widely adopted in the United States. Studies conducted on Japanese and East Asian patients with gastrointestinal malignancies combining CA72-4 with CEA and CA19-9 has shown useful disease correlation, with sensitivity of up to 74% without impairing specificity.
CEA. A 180-kDa oncofetal cell-surface-anchored glycoprotein, CEA was first isolated in 1965 by investigators at McGill University from human colon tissue extracts. The glycoprotein, with a half-life of approximately 7 days, was found to be expressed in gastrointestinal and mucosal tissue during fetal development but only minimally expressed in adult tissue. Further studies showed that it was also overexpressed in adenocarcinomas of varying origin including gastric, hepatic, lung, pancreatic, ovarian and prostate. In colon cancer, the specificity and sensitivity of CEA has been shown to vary with advancing tumor stage, with specificity ranging between 37% and 86% in advanced disease, providing a useful means of monitoring disease. CEA may also be elevated in benign conditions such as inflammatory bowel disease, pancreatitis and in smokers, limiting its utility in early-stage cancer and in patients with such conditions.
CA125. Encoded by the MUC16 gene, CA125 is a member of the mucin family of glycoproteins and is normally expressed in developing fetal epithelial lining of the body cavities and the female reproductive tract. The protein was first discovered by Dr. Robert Bast and other investigators at Harvard Medical School in 1981 after murine monoclonal antibodies were found to have reactivity with human epithelial ovarian carcinoma but not with non-malignant human tissues. CA125 is also associated with malignancies of the endometrium, fallopian tube, breast, lung, esophageal, gastric, hepatic and pancreatic cancers. Elevations in CA125 have also been observed in non-malignant conditions such as during menses, late pregnancy, episodes of serosal irritation such as endometriosis, benign follicular ovarian cysts, and conditions associated with inflammation such as pelvic inflammatory disease, peritonitis, ascites, pericarditis and pleural effusions. CA125 expression has been found to be positive in up to 83% of patients with advanced epithelial ovarian cancer but only in 50% of patients with stage 1 disease, thus limiting its role in ovarian cancer screening in the general population.
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