(Cancer Antigen 125)
Cancer antigen 125 (CA125) is a membrane mucin-like glycoprotein greater than 200 kDa. The specific function is unknown. In foetal tissue, CA125 is expressed in the amnion, coelomic and mullerian epithelium. In adult tissue CA125 is primarily expressed in mesothelial cells and in the luminal surface of epithelial cells of the fallopian tube, endometrium and endocervix. CA125 is also found in small amounts in various other epithelia such as pancreas, colon, biliary tract, stomach, apocrine sweat glands and mammary glands. CA125 is not expressed in normal ovarium and not in squamous epithelium.
CA125 is expressed in almost all cases of (epithelial) malignant mesothelioma and ovarian serous adenocarcinoma. CA125 is also expressed in the majority of primary peritoneal carcinoma and ovarian clear cell and endometrioid adenocarcinomas, while less than half of the mucinous adenocarcinomas are stained. Moreover, CA125 is expressed in most adenocarcinomas of fallopian tube, endometrium and endocervix as well as pancreas and biliary tract. A proportion of adenocarcinomas from lung, breast, thyroid and stomach also stain for CA125. CA125 is only rarely found in colorectal and prostatic adenocarcinoma, renal cell carcinoma, and embryonal carcinoma. Among non-epithelial tumours, CA125 may be found in epithelioid sarcoma and desmoplastic small round cell tumour.
CA125 is primarily used for the identification of malignant mesothelioma and serous ovarian carcinoma (where a negative staining speaks strongly against these diagnoses), but due to the rather wide distribution of CA125 the antibody should be included in a panel. CA125 may also be useful in the differentiatial diagnosis of ovarian clear cell carcinoma versus clear cell renal cell carcinoma, and of epithelioid sarcoma and desmoplastic small round cell tumour (which are positive) versus other mesenchymal tumours (virtually always negative).
Normal salpinx is a recommendable positive control: Virtually all the epithelial cells must show a moderate to strong, distinct membranous staining.
Selected references
Keen CE, Szakacs S, Okon E et al. CA125 and thyroglobulin staining in papillary carcinomas of thyroid and ovarian origin is not completely specific for site of origin. Histopathology. 1999; 34:113-117. Loy TS, Quesenberry JT, Sharp SC. Distribution of CA125 in adenocarcinomas: an immunohistochemical study of 481 cases. Am J Clin Pathol 1992;98:175–9. Attanoos RL, Webb R, Dojcinov SD, Gibbs AR. Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. Histopa-thology. 2002 Mar; 40(3): 237-44. Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ. Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagno-sis between colonic and ovarian carcinomas as primary sites. Hum Pathol. 1998 May; 29(5): 491-7. Kato H, Hatori M, Kokubun S, Watanabe M, Smith RA, Hotta T, Ogose A, Morita T, Murakami T, Aiba S. CA125 expression in epithelioid sarcoma. Jpn J Clin Oncol. 2004 Mar;34(3):149-54. McCluggage WG. Recent advances in immunohistochemistry in the diagnosis of ovarian neoplasms. J Clin Pathol. 2000 May; 53(5): 327-34. Nap M. Immunohistochemistry of CA 125. Unusual ex-pression in normal tissues, distribution in the human fetus and questions around its application in diagnostic pathol-ogy. Int J Biol Markers. 1998 Oct-Dec; 13(4): 210-5. Ordonez NG, Sahin AA. CA 125 production in desmo-plastic small round cell tumor: report of a case with ele-vated serum levels and prominent signet ring morphology. Hum Pathol. 1998 Mar; 29(3): 294-9. Yin BW, Dnistrian A, Lloyd KO. Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int J Cancer. 2002 Apr 10; 98(5): 737-40.
05.07.10 - SN/MV/LE