carcinoembryonic antigen

**Nature:** CEA is a ~180-200 kDa glycoprotein of the immunoglobulin superfamily (CEACAM5), anchored to the cell surface by a GPI anchor. It functions in cell-cell adhesion. It is an "oncofetal antigen": expressed in fetal gut, pancreas, and liver, with levels falling markedly after birth. It is re-expressed in certain malignancies.

**Clinical uses (high-yield):** - **Colorectal cancer (CRC):** The classic association. Used for (1) a preoperative baseline, (2) postoperative surveillance for recurrence (a rising level suggests recurrence or metastasis, especially to the liver), and (3) monitoring response to therapy. A persistently elevated level after resection suggests residual disease. A high preoperative level carries a worse prognosis. - **Not for screening:** It has poor sensitivity for early-stage disease and poor specificity, so it is not used for screening or primary diagnosis. - **Other malignancies with elevated CEA:** Gastric, pancreatic, breast, lung (especially adenocarcinoma and small cell), medullary thyroid carcinoma (also used to follow disease along with calcitonin), and ovarian mucinous tumors.

**Benign causes of elevation (false positives):** - Smoking (the most common cause of mild elevation) - Inflammatory bowel disease - Pancreatitis - Cirrhosis and other liver disease - Peptic ulcer disease - Diverticulitis - Chronic obstructive pulmonary disease - Hypothyroidism - Biliary obstruction (reduced clearance)

**Metabolism:** It is cleared by the liver (Kupffer cells), so hepatic dysfunction can raise levels.

**Board pearls:** - Tumor marker mnemonic: CEA = colorectal (also pancreatic); AFP = hepatocellular carcinoma and yolk sac tumor; CA 19-9 = pancreatic; CA-125 = ovarian (serous); PSA = prostate; calcitonin = medullary thyroid; S-100 = melanoma and neural crest tumors; β-hCG = choriocarcinoma and hydatidiform mole. - Tumor markers are generally used to monitor therapy and recurrence, not to diagnose (diagnosis requires tissue biopsy). - A patient with CRC who had a curative resection and now has a rising CEA should be evaluated with imaging (CT chest/abdomen/pelvis) and colonoscopy for recurrence. - Smokers can have mildly elevated baseline CEA, so interpret trends rather than single values. - CEA is also expressed on some bacteria-binding pathways: CEACAM receptors serve as binding sites for pathogens such as Neisseria and Haemophilus (a lower-yield fact). - In CRC, CEA is also used in adjunct to staging (it is a prognostic factor in the AJCC staging system). - Anti-CEA antibodies are used in imaging and are being explored as targets for CAR-T and other immunotherapies.