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PLoS One. 2016 Nov 9;11(11):e0166067. doi: 10.1371/journal.pone.0166067. eCollection 2016.

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

Author information

1
Department of Laboratory Medicine (LABMED) Division of Pathology, Karolinska Institute, Stockholm, Sweden.
2
Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden.
3
Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
4
Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.
5
Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
6
School of Electronic Engineering and Computer Science, Queen Mary University of London, London, United Kingdom.
7
Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institute, Stockholm, Sweden.
8
Service of Pathology, Ospedale Fatebenefratelli "S. Giovanni Calibita", Rome, Italy.

Abstract

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.

PMID:
27829047
PMCID:
PMC5102456
DOI:
10.1371/journal.pone.0166067
[Indexed for MEDLINE]
Free PMC Article

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