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Reviewer: Nat Pernick, M.D., PathologyOutlines.com, Inc. (see Reviewers page)
Revised: 21 November 2011, last major update August 2011
Copyright: (c) 2011, PathologyOutlines.com, Inc.


● Cancer antigen 125 (CA-125) is a protein encoded by MUC16 gene, used as a tumor marker, because it is 79% sensitive for ovarian cancer
● Not specific, because elevated in other tumors and in inflammatory conditions


● Also known as MUC16


● High molecular weight membrane associated mucin found in cornea and conjunctiva, in respiratory tract and female reproductive tract epithelium
● As a mucin, forms lubricating barrier against foreign particles and infectious agents

Clinical features

● Elevated in carcinomas of breast, cervix (Asian Pac J Cancer Prev 2010;11:1745), endometrium, fallopian tubes, GI, lung, ovary; also endometriosis, pregnancy, inflammatory disorders


● Strong membranous staining, fallopian tube is good control


● (1) For ovarian carcinomas, use serum levels to follow response to treatment and predict prognosis (Ann Oncol 2008;19:327)
● (2) In UK, recommended to use serum levels to screen women with symptoms of ovarian cancer (National Health Service Press Release)
● (3) Serial measurements may be more specific for ovarian cancer
● (4) Useful in immunohistochemistry to confirm ovarian origin of tumor (Am J Surg Pathol 2005;29:1482)
● (5) Serum levels may have role in assessing heart failure (Clin Cardiol 2011;34:244, Eur Heart J 2010;31:1752)

● High serum CA-125 levels are due to serosal fluids and serosal involvement of various diseases of ovarian or non-ovarian origin (Gynecol Oncol 2002;85:108)
● Serum levels not recommended for general low-risk ovarian cancer screening due to lack of sensitivity, particularly for low stage tumors (only 50% sensitive for stage I)

Micro images

Normal mesothelium

Various images and quality control

Ovarian carcinomas (CA125 is also called MUC16)

Epithelioid sarcoma

Micropapillary carcinoma-urinary tract

Mucinious cystic neoplasm of mesentery

Seminal vesicle adenocarcinoma

Positive staining - normal

● Fetus: amnion, coelomic and mullerian epithelium (Asia Oceania J Obstet Gynaecol 1990;16:379)
● Adults: mesothelial cells and luminal surface of epithelial cells of endocervix, endometrium, fallopian tube; also in small amounts in epithelium of apocrine sweat glands, biliary tract, colon, mammary gland, pancreas, stomach

Positive staining - disease

● Carcinomas of biliary tree, breast, cervix, endometrium, fallopian tubes, liver, lung, ovary (serous, usually not mucinous), pancreas; ovarian sex cord tumors
● Alveolar rhabdomyosarcoma of uterus, desmoplastic small round cell tumor of pelvic peritoneum, epithelioid sarcoma (Arch Pathol Lab Med 2006;130:871, Jpn J Clin Oncol 2004;34:149), intralobar pulmonary sequestration (Intern Med 2002;41:875), leiomyoma of ileal mesentery, mesothelioma,seminal vessel adenocarcinoma
● Endometriosis (Hum Pathol 2008;39:954), inflammatory disorderes, leiomyomas of ileal mesentery, pregnancy

Negative staining

● Normal ovary, squamous cells

End of Stains > CA125

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