What is CA 15-3?
CA 15-3 is a glycoprotein derived from the MUC1 membrane of the mucin family, also known as polymorphic epithelial mucins (PEMs) or epithelial membrane antigens (EMAs). CA 15-3 binds to oligosaccharides on pathogens, helping to prevent their interaction with the cell surface. In addition to its role in the body’s defense, it is crucial for cell signaling, enabling cells to detect and respond to signals from their environment.1
While CA 15-3 levels below 30 units per milliliter (U/mL) occur naturally in healthy individuals, some, such as women during pregnancy and lactation, may experience levels exceeding the CA 15-3 normal range. However, most often, an elevated volume of the cancer antigen in blood serum, or an atypical pattern of sugar molecules (glycans), often signals abnormalities, including certain types of cancer. The correlation between CA 15-3 levels in blood serum and tumor size has made it a useful cancer marker.2
Health conditions that can elevate CA 15-3 levels
Some oncologic conditions, particularly advanced-stage tumors, tend to increase the production of CA 15-3, raising its levels above normal. Breast, ovarian, and endometrial cancers, along with tumors in the lungs, liver, colon, and pancreas, are especially known for elevating CA 15-3 levels in the blood.
However, increased CA 15-3 levels are not always indicative of cancer. Other health conditions that can affect the production of this protein include:
- Benign breast disease
- Systemic lupus erythematosus
- Pelvic inflammatory disease
- Endometriosis
- Liver cirrhosis
- Chronic hepatitis
- Tuberculosis
- Sarcoidosis
Cancer antigen CA 15-3 blood test
The variety of factors affecting CA 15-3 levels in blood serum makes it a less reliable marker for cancer detection. Besides non-cancerous conditions that can interfere with CA 15-3 testing, some patients may have normal CA 15-3 levels despite the presence of a tumor, especially in its early stages. Additionally, some cancer cells may not produce elevated levels of CA 15-3 at all, further limiting the test’s effectiveness.
Despite its limitations for screening, CA 15-3, when combined with other clinical information, can be useful for determining cancer stage, treatment response, and recurrence. One of its most common practical applications is monitoring the progression of breast cancer.
The specific routine for collecting blood samples and assessing CA 15-3 tumor marker levels may vary depending on the healthcare provider and laboratory. A common approach involves drawing a blood sample from a vein, separating the serum (the liquid part), and then analyzing the serum using a chosen immunoassay technique. These techniques may include:
- Radioimmunoassay (RIA), which uses radioactive isotopes to label CA 15-3;
- Electrochemical immunoassay, measuring the electrical current generated by the interaction between antibodies and CA 15-3;
- Enzyme-linked immunosorbent assay (ELISA), which detects CA 15-3 using enzyme reactions.
For higher accuracy, a CA 15-3 blood test is often combined with other tests, including Her2/neu, estrogen and progesterone receptor tests, and BRCA1 and BRCA2 genetic testing.
An alternative test based on the MUC1 protein is CA 27.29. It is reported to be more sensitive for detecting primary breast cancer but is less available because the antibody it uses is patented by Siemens.3
References:
- Bon GG et al. “Clinical and technical evaluation of ACS™BR serum assay of MUC1 gene-derived glycoprotein in -breast cancer, and comparison with CA 15-3 assays.” Clinical Chemistry. 1997. 43(4):585-593.
https://academic.oup.com/clinchem/article/43/4/585/5640902 - Metkar SK, Girigoswami K, “Diagnostic biosensors in medicine – A review.” Biocatalysis and Agricultural Biotechnology. 2019.
https://www.sciencedirect.com/topics/immunology-and-microbiology/ca-15-3-antigen - Gion M, Mione R, Leon A E, Dittadi R, “Comparison of the diagnostic accuracy of CA27.29 and CA15.3 in primary breast cancer.” American Association for Clinical Chemistry. 1999.
https://pubmed.ncbi.nlm.nih.gov/10222349/