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.
Methods
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.
Results
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.
Conclusions
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.
Citation: Fernández Moro C, Fernandez-Woodbridge A, Alistair D'souza M, Zhang Q, Bozoky B, Kandaswamy SV, et al. (2016) Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification. PLoS ONE 11(11): e0166067. doi:10.1371/journal.pone.0166067
Editor: Francisco X. Real, Centro Nacional de Investigaciones Oncologicas, SPAIN
Received: June 17, 2016; Accepted: October 8, 2016; Published: November 9, 2016
Copyright: © 2016 Fernández Moro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The complete dataset, code and reproducible computer environment for the analysis, including a Docker image are provided on-line: doi:10.5061/dryad.g8h71.
Funding: This study was supported by grants from the Stockholm County Council (ALF), the Swedish Cancer and Allergy Foundation, and the Research Funds of the Radiumhemmet, Stockholm.
Competing interests: The authors have declared that no competing interests exist.
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