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Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification

posted on 09.11.2016, 17:40 by Carlos Fernández Moro, Alejandro Fernandez-Woodbridge, Melroy Alistair D'souza, Qianni Zhang, Benedek Bozoky, Senthil Vasan Kandaswamy, Piera Catalano, Rainer Heuchel, Sonia Shtembari, Marco Del Chiaro, Olof Danielsson, Mikael Björnstedt, J. Matthias Löhr, Bengt Isaksson, Caroline Verbeke, Béla Bozóky

Background & Aims

Adenocarcinomas of the pancreatobiliary system are currently classified by their primary anatomical location. In particular, the pathological diagnosis of intrahepatic cholangiocarcinoma is still considered as a diagnosis of exclusion of metastatic adenocarcinoma. Periampullary cancers have been previously classified according to the histological type of differentiation (pancreatobiliary, intestinal), but overlapping morphological features hinder their differential diagnosis. We performed an integrative immunohistochemical analysis of pancreato-biliary tumors to improve their diagnosis and prediction of outcome.


This was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed.


Hierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05–0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type.


Integrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic immunohistochemical panel and additional extended panels of discriminant markers are proposed as guidance for their pathological diagnosis.