Cytokeratin is a superior marker for detection of micrometastatic biliary tract carcinoma

Abstract

Background: The incidence of lymph node micrometastases in patients with biliary tract carcinoma is unknown. We evaluated the utility of three antibodies for immunohistochemical (IHC) detection of micrometastatic disease in patients with gallbladder and bile duct carcinoma.

Materials and methods: Surgical specimens from 35 patients with biliary tract carcinoma were evaluated. Histologically involved tissues were stained with the following antibodies using standard IHC techniques: cytokeratin (AE1:AE3), CEA (carcinoembryonic antigen), and EMA (epithelial membrane antigen). The antibodies with the greatest degree of positive staining were then used to evaluate the lymph nodes of patients with histologically negative lymph nodes. Micrometastatic disease was defined as clustered atypical cells <2 mm in size detected only with the use of IHC.

Results: All of the primary tumors and histologically positive lymph nodes demonstrated staining with cytokeratin and CEA antibodies, whereas only 83% were positive for EMA. Therefore, cytokeratin and CEA antibodies were used to evaluate histologically negative lymph nodes. Anti-cytokeratin immunostaining detected micrometastatic disease in two patients. Staining with anti-CEA was negative in all specimens. Overall, two of 15 patients with histologically node negative biliary tract carcinoma had occult micrometastases.

Conclusion: Cytokeratin immunostaining enables detection of micrometastases in histologically negative lymph nodes in patients with biliary tract carcinoma. Prospective protocols incorporating cytokeratin staining of the lymph nodes may help determine the incidence and clinical significance of occult micrometastatic disease in these patients.