Expression of integrin ανβ6 differentiates perihilar cholangiocarcinoma (PHC) from benign disease mimicking PHC

L.C Franken,F.A Vuijk,E.C Soer,E Roos,J.I Erdmann,G.K.J Hooijer,A.L Vahrmeijer,S.S Gambhir,T.M Van Gulik,A Farina Sarasqueta,J Verheij,R.J Swijnenburg

doi:10.1016/j.ejso.2020.09.026

Abstract

BackgroundApproximately 15% of patients undergoing resection for presumed perihilar cholangiocarcinoma (PHC) have benign disease at final pathological assessment. Molecular imaging targeting tumor-specific biomarkers could serve as a novel diagnostic tool to reduce these futile surgeries. Imaging agents have been developed, selectively binding integrin ανβ6, a cell receptor upregulated in pancreatobiliary malignancies, for both (preoperative) PET and (intraoperative) fluorescent imaging. Here, expression of integrin ανβ6 is evaluated in PHC, intrahepatic cholangiocarcinoma (ICC), hepatocellular carcinoma (HCC) and benign disease mimicking PHC using immunohistochemistry. Materials & methodsThree tissue microarrays (TMA) including 103 PHC tumor cores and sixty tissue samples were selected from resection specimens of pathologically proven PHC (n = 20), ICC (n = 10), HCC (n = 10), metastatic PHC lymph nodes (n = 10) and benign disease (presumed PHC with benign disease at pathological assessment, n = 10). These samples were stained for integrin ανβ6 and quantified using the H-score. ResultsImmunohistochemical staining for integrin ανβ6 showed membranous expression in all twenty PHC whole mount slides (100%) and 93 out of 103 (92%) PHC tumor cores. Mean H-score of PHC samples was 195 ± 71, compared to a mean H-score of 126 ± 57 in benign samples (p = 0.013). In both benign and PHC samples, inflammatory infiltrates and pre-existent peribiliary glands showed integrin ανβ6 expression. The mean H-score across ten ICC was 33 ± 53, which was significantly lower compared to PHC (p < 0.001) but too weak to consistently discriminate ICC from HCC (H-score 0)(p = 0.062). ConclusionIntegrin ανβ6 is abundantly expressed in PHC and associated metastatic lymph nodes. Expression is significantly higher in PHC as compared to benign disease mimicking PHC, ICC and HCC, emphasizing its potential as a target for tumor-specific molecular imaging.

Highlights

Perihilar cholangiocarcinoma (PHC) is a tumor originating from the bile duct epithelium at the liver hilum, with an annual incidence of approximately 2 cases per 100.000 in the West [1].specimen [4]
Expression of integrin anb6 is evaluated in perihilar cholangiocarcinoma (PHC), intrahepatic cholangiocarcinoma (ICC), hepatocellular carcinoma (HCC) and benign disease mimicking PHC using immunohistochemistry
All of ten (100%) PHC metastases in lymph nodes stained positive for integrin anb6 with a mean H-score of 169 ± 84, whilst all tumor-negative lymph nodes showed no expression of integrin anb6 (p < 0.001)(Fig. 1b)

Summary

Introduction

Perihilar cholangiocarcinoma (PHC) is a tumor originating from the bile duct epithelium at the liver hilum, with an annual incidence of approximately 2 cases per 100.000 in the West [1].specimen [4]. Materials & methods: Three tissue microarrays (TMA) including 103 PHC tumor cores and sixty tissue samples were selected from resection specimens of pathologically proven PHC (n 1⁄4 20), ICC (n 1⁄4 10), HCC (n 1⁄4 10), metastatic PHC lymph nodes (n 1⁄4 10) and benign disease (presumed PHC with benign disease at pathological assessment, n 1⁄4 10). These samples were stained for integrin anb and quantified using the

Methods

Results

Conclusion