• CEA is a glycoprotein normally found in embryonic entodermal epithelium
• Exhibits heterogeniety carbohydrate side chains • Liver primary site for metabolism of CEA • It is suggested that it might act as an adhesion molecule – Number of liver metastases increased from 2% to 48% after injection of nude mice with CEA – Localized in the apical surface of mature enterocytes & bind certain E. coli strains • Present in other neoplastic and non neoplastic conditions Capture antibody PRINCIPLE
• Specimen: Clotted blood (Serum) Antigen
• Circulatory half-life: ~7 days • Two-site sandwich immunoassay using two antibodies – Capture antibody: Monoclonal mouse anti-CEA antibody covalently coupled to paramagnetic particles – Antigen: Serum containing CEA – Detection antibody: Purified polyclonal Detection rabbit anti-CEA antibody labeled with antibody acridinium ester • Colorimetric response: Spectrophotometer
Normal values: <2.5 ng/ml and for a smoker <5.0 ng/ml
FACTORS AFFECTING SERUM CEA CONCENTRATIONS IN PATIENTS WITH COLORECTAL CANCER Tumor stage Increased values with increasing disease stage
Tumor grade Increased with well-differentiated tumors than
poorly differentiated tumors Liver status Certain benign liver diseases can impair clearance of CEA Tumor site within the colon Left sided tumors have higher incidence of increased CEA than right sided tumors Presence or absence of bowel Bowel obstruction per se can cause increase in obstruction CEA & decompression can reduce CEA Smoking Approximately doubles serum CEA concentration Ploidy status of tumor Aneuploid CRC produce higher CEA concentrations than those with a near diploid pattern CEA as a marker for colorectal cancer • SCREENING – Sensitivity at 5ng/ml: 52%; – For Dukes A and B at 2.5ng/ml: 68.7% – Upper limit of normal 2.5 ug/L – Sensitivity: 36% – Specificity at 5ng/ml: – Specificity: 87% 76.98%; at 10ng/ml: 86% – vs HSFBT: Sen > 70%; Spec: >90% • PROGNOSIS – College of American Pathologists Expert Groups: preoperative serum • DIAGNOSIS CEA concentration – Category I – Benign diseases rarely give rise to prognostic marker for CRC > 10ug/L – High concentration 1-3 months after hepatectomy = adverse – > 5x upper limit of normal – prognosis strongly suggestive of cancer CEA as a marker for colorectal cancer • SURVEILLANCE • MONITORING CHEMOTX IN – Longitudinal CEA measurements PATIENTS WITH ADVANCED for recurrent ds DISEASE • Sensitivity: ~80% – American Society of Clinical • Specificity: ~70% Oncology Panel: – Serial CEA measurement for liver • Baseline CEA value before metastasis treatment • Sensitivity: 94%, • Serial monitoring every 2-3 • Specificity: 96% months – Can detect recurrent CRC with an average lead time of 5 months update
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