CA-125

**What it is:** CA-125 (cancer antigen 125) is a high-molecular-weight glycoprotein, encoded by the MUC16 gene, expressed on cells derived from coelomic epithelium (Müllerian derivatives, peritoneum, pleura, pericardium).

**Clinical uses (high-yield):** - Monitoring response to therapy and detecting recurrence in epithelial ovarian cancer (especially serous carcinoma). A falling level after surgery/chemo suggests response, and a rising level suggests relapse. - Adjunct in evaluating an adnexal/pelvic mass, particularly in postmenopausal women, often combined with transvaginal ultrasound (e.g., Risk of Malignancy Index, ROMA). - Not recommended for general population screening. Low sensitivity for early-stage disease (about 50% in stage I) and low specificity lead to false positives and unnecessary surgery. It may be used with TVUS in high-risk patients (BRCA1/2, Lynch syndrome), but evidence of mortality benefit is lacking.

**Causes of elevation (non-malignant, a classic exam trap):** - Endometriosis (often markedly elevated, but its main role is monitoring) - Menstruation, pregnancy (first trimester) - Pelvic inflammatory disease - Uterine fibroids, adenomyosis - Peritonitis, ascites, cirrhosis, heart failure (serosal irritation) - Pleural or pericardial effusions - Benign ovarian cysts

**Other malignancies with elevation:** endometrial, fallopian tube, primary peritoneal, pancreatic, breast, lung, GI (colon) cancers.

**Ovarian tumor marker associations (for comparison):** - Serous/epithelial: CA-125 - Dysgerminoma: LDH (also placental ALP) - Yolk sac (endodermal sinus) tumor: AFP (Schiller-Duval bodies) - Choriocarcinoma: β-hCG - Sertoli-Leydig and granulosa cell tumors: inhibin (granulosa: Call-Exner bodies) - Mucinous: CEA, CA 19-9 - Struma ovarii: thyroid hormone

**Key concept:** Tumor markers are generally used for monitoring and prognosis, not for diagnosis or screening. Tissue biopsy/histology is required for definitive diagnosis.

**Risk factors for ovarian cancer (context):** nulliparity, early menarche/late menopause (more ovulatory cycles), BRCA1/2 mutations, Lynch syndrome, and family history. OCP use and multiparity are protective.