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

Abstract

Background & AimsAdenocarcinomas 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.MethodsThis 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.ResultsHierarchical 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.ConclusionsIntegrative 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.

Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis

“…Some sources detail only two immunophenotypes of IPNBs: the “pancreatic” which is more similar to IPMN and the “non-pancreatic” with frequent high-grade dysplasia (papillary CC) [123,135]. Using the hierarchical clustering and differential IHC analysis for adenocarcinomas of the pancreatobiliary system, three IHC tumour subtypes were identified, namely: extrahepatic pancreatobiliary, intestinal and intrahepatic CC [136].…”

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

“…When looking at the most upregulated proteins identified in our study, several proteins, such as protein S100-P [ 63 , 64 ], carcinoembryonic antigen-related cell adhesion molecule 6 [ 65 ], keratin, type I cytoskeletal 17 [ 66 , 67 ], thymidine phosphorylase [ 68 , 69 ], heat shock protein 90 alpha/beta [ 70 ] and olfactomedin-4 [ 71 , 72 ], are well established as upregulated proteins and tentative biomarkers in CCA. The correct identification and quantification of known biomarkers gives us confidence in the biological relevance of the proteins identified with our study design.…”

Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor

“…Indeed, MUC16 (cancer antigen 125, CA 125) is used in clinics to diagnose and predict prognosis in ovarian cancer patients, but it is also upregulated in a large percentage of digestive tract adenocarcinomas and has been proposed as a prognostic marker for gastrointestinal cancers [63]. In a recent study, positive immunohistochemical staining of MUC16 (immunoreactivity in more than 10% of the tumor cells) was observed in more than 75% of extrahepatic pancreatobiliary tumors (n = 234 cases), including 37 gallbladder cancers [64]. Chaube et al proposed MUC16 as a potential diagnostic marker because serum levels are increased in patients with GBC and benign disease can be differentiated from malignant disease with a sensitivity of 64% and a specificity of 90% [65].…”