Neuroendocrine differentiation and prognosis of extrahepatic biliary tract carcinomas

From 1980 to 1987, 35 patients underwent exploratory surgery for carcinomas of the extrahepatic biliary tract (EBT). Samples from 28 of these tumors (15 gallbladder, 13 bile duct) were assessed by immunohistochemical analysis for exocrine and/or neuroendocrine differentiation. Seven patients were excluded from the study because of insufficient available specimen or loss to follow-up. Paraffin sections were immunostained for neuroendocrine differentiation markers: neuron-specific enolase (NSE), chromogranin-A, synaptophysin, serotonin, somatostatin, substance-P, and glucagon. Additional sections were also stained with monoclonal antibody A-80 that recognizes a glycoprotein related to exocrine differentiation. The tumors were reclassified on the basis of immunophenotyping data: (I) pure exocrine carcinoma (n = 8); (II) predominantly exocrine carcinoma with occasional neuroendocrine cells (n = 9); (III) mixed exocrine-neuroendocrine carcinoma (n = 4); (IV) pure neuroendocrine (n = 2); and (V) predominantly neuroendocrine with occasional exocrine cells (n = 5). Survival time among the two pure neuroendocrine (group IV) and five predominantly neuroendocrine carcinomas (group V) was significantly less than the survival time of patients from the other groups (2.6 +/- 2.2 months vs 13.5 +/- 12.3 months; p = 0.015). No difference was noted between groups in extent of disease, treatment rendered, or location of tumor (bile duct vs gallbladder). This study indicates that (1) the incidence of neuroendocrine differentiation in cancers of the EBT is higher than generally recognized, (2) carcinomas of the EBT may be phenotypically reclassified on the basis of immunohistochemical analysis, and (3) the presence of pure or predominant neuroendocrine differentiation in carcinomas of the EBT is associated with shorter survival time than carcinomas with pure or predominant exocrine differentiation (or mixed exocrine and neuroendocrine factors).