CA 125

Dako (OC125) and Immunotech (Ov185).

Monoclonal anti-CA 125 (M11) can be used on formalin-fixed, paraffin-embedded tissue sections. The deparaffinized tissue sections must be treated with heat (in citrate buffer or Dako Target Retrieval Solution) prior to the immunohistochemical staining procedure.

CA 125 was discovered with a monoclonal screen for tumor-specific antigens of hybridomas derived from mouse lymphocytes immunized to an ovarian cell culture line, OVCA433 (Bast et al, 1981). The antigen is located on the surface of ovarian tumor cells with essentially no expression in normal adult ovarian tissue (Kabawat et al, 1983). Significantly, CA 125 is also found in sera of patients with ovarian, pancreatic (about 50%), liver, colon and other (22%-32%) adenocarcinomas (Kuzuya et al, 1986). Although CA 125 is not specific for ovarian carcinoma, it nevertheless does correlate directly with disease status (Bast et al, 1983). Similar to other tumor markers, CA 125 is also expressed normally in fetal development: the antigen has been localized to the amnion celomic epithelium and derivatives of MUlerian epithelium (Hardardottir et al, 1990). In adult tissue, the monoclonal antibody OC 125 reacted with the epithelium of the fallopian tube, endometrium, endocervix, apocrine sweat glands and mammary glands (Kabawat et al, 1990; Hardardottir et al, 1983; O'Brien et al, 1991).
Presently, little is known of the structure of this extracellular matrix molecule, nor is there any indication of its function. It appears to be part of a large molecular weight mucin-like glycoprotein complex that can be resolved to a 200-250 kD species on gel electrophoresis. Although the antigen is thought to contain a carbohydrate component, the antigenic epitope recognized by OC 125 is considered to be peptide in nature (Davis et al, 1986).

The most important property of CA 125 is that it is regularly expressed on the tumor cell surface of serous cystadenocarcinoma of the ovary (>95%), whilst no expression is detected in mucinous cystadenocarcinomas. Although only a small number of tumors were examined, the following were also found to stain positively with CA 125: colonic adenocarcinoma (1/2), breast carcinoma (3/8), uterine papillary serous carcinoma (1/1), thyroid follicular adenoma (1/1), transitional cell carcinoma of the bladder (2/3), uterine adenomatoid tumor (1/1), lung bronchoalveolar carcinoma (1/1), endometrioid carcinoma of the ovary (2/2) and squamous cell carcinoma of the penis (1/1) (Dako specifications). Employed in an appropriate panel, CA 125 is useful for the separation of colonic carcinoma from ovarian endometrioid carcinoma in the pelvis (Appendix 1.13). Recently, a mesothelioma was reported which demonstrated both serum and immunohistochemical positivity with CA 125 (Almudvar Bercero et al, 1997). This indicates that CA 125 cannot reliably distinguish between metastatic serous epithelial tumors of the peritoneum and mesothelioma.

The major role of CA 125 in immunohistology is in the identification of metastatic serous carcinoma of the ovary. Primary serous cystadenocarcinoma of the ovary is the recommended positive control tissue for optimization of CA 125.

•Bast RC Jr, Feeney M, Lazarus H, et al 1981. Reactivity of a monoclonal antibody with human ovarian carcinoma. Journal of Clinical Investigation 68: 1331-1337.

•Bast RC, Lug TL, St John E et al 1983. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. New England Journal of Medicine 309: 883-887.

•Almudvar Bercero E, Garc.-Rostan Y Prez GM, Garc. Bragado F, Jimnez C 1997. Prognostic value of high serum levels of CA-125 in malignant secretory peritoneal mesotheliomas affecting young women. A case report with differential diagnosis and review of the literature. Histopathology 31: 267-273.

•Davis AM, Zurawski VR, Bast RC, Klug TL 1986. Characterization of the CA 125 antigen associated with human epithelial ovarian carcinomas. Cancer Research 46: 6143-6148.

•Hardardottir H, Parmley TH, Quirk JG et al 1990. Distribution of CA 125 in embryonic tissues and adult derivatives of fetal periderm. American Journal of Obstetrics and Gynecology 163: 1925-1931.

•Kabawat SE, Bast RC, Bhan AK, et al 1983. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC 125. International Journal of Gynecologic Pathology 2:275-285.

•Kuzuya K, Nozaki M, Chihara T 1986. Evaluation of CA 125 as a circulating tumor marker for ovarian cancer. Acta Obstetric et Gynecologica Japan. 38: 949-957.

•O'Brien TJ, Raymond LM, Bannon GA, et al 1991. New monoclonal antibodies identify the glycoprotein carrying the CA 125 epitope. American Journal of Obstetrics and Gynecology 165: 1857-1864.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.