Mucin-like carcinoma-associated antigen (MCA)

MCA Overview

Mucin-like Carcinoma-Associated Antigen (MCA) is a high-molecular-weight glycoprotein that belongs to the family of epithelial mucins. These mucins are normally found on the surface of glandular epithelial cells, including those in the breast.

In certain cancers, particularly breast cancer, the expression and shedding of these mucins into the bloodstream can increase significantly. Measuring the level of MCA in the blood (serum) can therefore serve as a non-specific tumor marker, primarily used in the context of breast cancer.

Biology of MCA

MCA is characterized as a mucin-glycoprotein, meaning it is heavily glycosylated (has many sugar chains attached). Its molecular mass is substantial, typically ranging from 350 to 500 kDa (kilodaltons).

It is structurally related to other mucin tumor markers used in breast cancer diagnosis and monitoring, such as CA 15-3 and CA 27.29, all of which detect different epitopes (antigenic sites) on the MUC1 protein product. Overexpression and altered glycosylation of MUC1 are common features of breast carcinoma cells, leading to the shedding of these antigens into the circulation.

Clinical Indications for MCA Testing

The primary clinical indication for measuring MCA levels is:

1. Monitoring Disease Course in Breast Cancer: Assessing response to therapy and surveillance for recurrence or metastasis in patients previously diagnosed with breast cancer, particularly those with advanced disease. Changes in MCA levels over time are often more informative than a single measurement.
2. Prognostic Information (Limited): Some studies suggest that pre-treatment MCA levels may correlate with tumor stage and prognosis, but it is not routinely used for initial staging.

MCA is not recommended for screening asymptomatic women for breast cancer or for the initial diagnosis of breast cancer due to its limited sensitivity (especially in early stages) and specificity.

Interpretation of MCA Levels

Interpretation requires correlation with the patient's clinical status, imaging studies, and other diagnostic information.

• Normal Range: The upper limit of normal for MCA is typically cited as around 11 U/mL (Units per milliliter), though this specific threshold can vary depending on the laboratory and the assay kit used. Always consult the laboratory's specific reference range.
• Elevated Levels in Breast Cancer:
  • Elevated MCA levels are most commonly observed in patients with metastatic or advanced breast cancer.
  • The degree of elevation often correlates with the tumor burden and stage of the disease – higher levels are more likely with more extensive disease.
  • A significant rise in serial MCA measurements may indicate disease progression or recurrence, potentially preceding clinical or radiological evidence.
  • A significant decrease in MCA levels following therapy (surgery, chemotherapy, hormonal therapy, radiation) suggests a positive treatment response.

Factors Affecting MCA Levels

Elevated MCA levels are not exclusive to breast cancer and can be seen in other conditions:

• Other Malignancies: Elevations can sometimes occur in other adenocarcinomas, such as ovarian, lung, or gastrointestinal cancers, although MCA is less commonly used for these.
• Benign Conditions:
  • Benign breast disease (mastopathy): Mild elevations can be seen in some cases (reportedly up to 20% in the original text).
  • Benign liver diseases (e.g., cirrhosis, hepatitis): Mild elevations reported in about 20% of cases.
  • Other inflammatory conditions.
• Pregnancy: MCA levels can become elevated during pregnancy, particularly from the second trimester onwards (starting around the 4th month according to the original text).

These non-malignant causes contribute to the test's lack of specificity for initial diagnosis.

Limitations & Combination Testing

• Specificity: Elevations can occur in benign conditions and pregnancy.
• Sensitivity: Often normal in early-stage breast cancer, limiting its use for early detection or diagnosis.
• Monitoring Focus: Primarily useful for monitoring diagnosed patients with elevated baseline levels.
• Combination with Other Markers:
  • Combining MCA with other breast cancer markers like CA 15-3 or CA 549 (which often measure related epitopes on the MUC1 protein) is generally not considered to significantly improve overall diagnostic sensitivity beyond using one marker alone.
  • Combining MCA with a less specific but broadly elevated marker like Carcinoembryonic Antigen (CEA) might potentially increase sensitivity for detecting recurrence or progression in some patients, as they reflect different biological aspects.

The MCA Blood Test Procedure

• Sample Type: Blood serum.
• Preparation: No special patient preparation, such as fasting, is typically required.
• Collection: Standard venipuncture to draw a blood sample from a vein in the arm.
• Analysis: Measured in a clinical laboratory using immunoassays (e.g., ELISA, chemiluminescence).

References

1. Duffy, M. J. (2001). CA 15-3 and related mucins as circulating markers in breast cancer. *Annals of Clinical Biochemistry*, 38(Pt 6), 579–586. https://doi.org/10.1258/0004563011900890 (Discusses related MUC1 markers)
2. Eskelinen, M., Hippeläinen, M., Kettunen, J., Salmela, E., Penttilä, I., & Alhava, E. (1992). Clinical value of serum tumour markers TPA, TPS, TAG 12, CA 15-3 and MCA in breast cancer diagnosis. *Anticancer Research*, 12(3), 799–803. (Example study comparing markers)
3. Sturgeon, C. M., Hoffman, B. R., Chan, D. W., Ch'ng, S. L., Hammond, E., Hayes, D. F., ... & Diamandis, E. P. (2008). National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in clinical practice: quality requirements. *Clinical Chemistry*, 54(8), e1–e10. https://doi.org/10.1373/clinchem.2007.094144 (General guidelines on tumor marker use)
4. Nicolini, A., Carpi, A., & Tarro, G. (2018). Biomarkers in Breast Cancer: Established and Novel Approaches. *Advances in Experimental Medicine and Biology*, 1026, 21–41. https://doi.org/10.1007/978-3-319-67685-6_2