CA125

Synonyms: Cancer Antigen 125, Carbohydrate Antigen 125

by Assia Bassarova

Background

Cancer antigen 125 (CA125) is a membrane large mucin-like glycoprotein with variable molecular weights due to variation in glycosylation. It is encoded by the MUC16 gene, located on the short arm of chromosome 19, at 19p13.3. The specific function is unknown.

Staining in normal tissues

  • Kabawat et al. demonstrated expression of the CA 125 antigen in 1st and 2nd trimester fetal tissues derived from the coelomic epithelium (Mullerian ducts, cells lining the fetal peritoneum, pleura and pericardium) and amniotic epithelium, but not cells lining the fetal ovary or any other fetal tissues
  • In adult tissue, CA125 is mainly expressed in mesothelial cells and in the luminal surface of epithelial cells of the fallopian tube, endometrium and endocervix. Based on these observations Kabawat et al. concluded that CA 125 is a differentiation antigen associated with coelomic epithelium and its normal and neoplastic derivatives
  • CA125 is also found in small amounts in various other epithelia such as pancreas, colon, biliary tract, stomach, apocrine sweat glands and mammary glands
  • Normal ovaries and squamous epithelium are CA125 negative

Staining in tumors

CA125 expression is observed in:

  • Almost all cases of epithelioid malignant mesothelioma but much less (30%) in sarcomatoid variant
  • Ovarian serous adenocarcinoma and ovarian clear cell and endometrioid adenocarcinomas
  • Mucinous ovarian adenocarcinomas are positive in less than half of the cases
  • Most adenocarcinomas of fallopian tube, endometrium and endocervix
  • Majority of primary peritoneal carcinomas, as well as pancreas and biliary tract adenocarcinomas
  • A minority (10-30%) of lung, breast, thyroid and stomach adenocarcinomas also stain for CA125
  • CA125 is only rarely found (<10%) in colorectal and prostatic adenocarcinoma, renal cell carcinoma, and embryonal carcinoma
  • Among non-epithelial tumors, CA125 may be found in epithelioid sarcoma and desmoplastic small round cell tumor (DSRCT)

Staining pattern

Strong, distinct membranous staining reaction.

Control tissue

Fallopian tube – the luminal surface of epithelial cells shows a moderate and distinct membranous staining.

Application

CA125 is quite sensitive but nonspecific marker useful in the panel:

  • Supporting diagnosis of serous ovarian carcinoma (together with WT1 and PAX8)
  • Positive staining may support possibility of malignant mesothelioma
  • Differential diagnosis of ovarian clear cell carcinoma versus metastatic clear cell renal cell carcinoma
  • In certain diagnostic context may support primary site of origin e.g. primary location in pancreas/bile ducts vs. other locations (colon, rectum, breast, lung)
  • Positivity in rare adenocarcinoma of seminal vesicle in addition to PAX8 positivity helps to distinguish this tumor from CA125 negative carcinomas in neighboring organs (prostate, rectum or urinary bladder)
  • Positive staining of epithelioid sarcoma and desmoplastic small round cell tumor may be useful in differential diagnosis against negative other mesenchymal tumors

Selected references

  1. Charkhchi P, Cybulski C, Gronwald J, et al. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel). 020;12(12):3730. Published 2020 Dec 11. doi:10.3390/cancers12123730
  2. Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989 Jan;4(1):1-12. doi: 10.1093/ oxfordjournals.humrep.a136832. PMID: 2651469.
  3. Kabawat SE, Bast Jr RC, Bhan AK, et al. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125.    Int J Gynecol Pathol. 1983;2(3):275-85. doi: 10.1097/00004347-198303000-00005. PMID: 6196309 DOI: 10.1097/00004347-198303000-00005