CEA

**Definition/Biology:** Carcinoembryonic antigen is a ~180-kDa cell-surface glycoprotein (immunoglobulin superfamily; CEACAM5) involved in cell adhesion. It is normally produced in fetal gut, pancreas, and liver tissue, with very low levels in adults. It is shed into blood from tumor cells, so serum levels rise in some malignancies.

**Clinical uses (high-yield):** - **Colorectal cancer**: the classic association. Obtain a preoperative baseline, then check postoperatively. A level that fails to normalize after resection suggests residual disease. A rising level during surveillance suggests recurrence or metastasis (especially liver). Surveillance is typically every 3-6 months for the first 2-3 years for stage II-III disease. It also has prognostic value, since a high preoperative level correlates with worse prognosis. - **Not for screening**: low sensitivity for early-stage disease and poor specificity. - Also elevated in: pancreatic, gastric, breast, lung (especially adenocarcinoma), medullary thyroid, and ovarian mucinous cancers.

**Non-malignant causes of elevation (false positives):** - Smoking (the most common cause of mild elevation) - Inflammatory bowel disease (especially ulcerative colitis) - Pancreatitis - Cirrhosis/hepatitis - Peptic ulcer disease - COPD - Diverticulitis - Hypothyroidism - Biliary obstruction - Advanced age

**Exam pearls:** - CEA = colorectal cancer recurrence monitoring. Compare other markers: - AFP: hepatocellular carcinoma, yolk sac tumor - CA 19-9: pancreatic cancer - CA-125: ovarian (epithelial) cancer - PSA: prostate cancer - β-hCG: choriocarcinoma, hydatidiform mole - Calcitonin: medullary thyroid carcinoma - S-100: melanoma, neural tumors - Tumor markers are generally used for monitoring and not for definitive diagnosis, which requires tissue biopsy. - CEA can also be elevated in medullary thyroid carcinoma along with calcitonin, and can be used to track it. - Rising CEA with a negative workup may prompt imaging (CT chest/abdomen/pelvis, PET) and colonoscopy. - Heterophilic antibodies or biotin can interfere with assays, so an unexpected result should be interpreted in clinical context. - Mucinous adenocarcinoma of the colon and the sigmoid/rectal location also commonly show CEA expression, and CEA levels may also be measured in cyst fluid to help distinguish mucinous pancreatic cysts (high CEA) from serous cystadenomas (low CEA).