Expression of integrin a?β6 to differentiate perihilar cholangiocarcinoma from benign disease: A pilot study.

Abstract

Background: Curative treatment for patients with perihilar cholangiocarcinoma(PHC) generally consists of extrahepatic bile duct resection with (extended)hemihepatectomy, an operation that is known for its high morbidity and mortality. Diagnostic tests are often lacking in establishing the diagnosis of PHC preoperatively; as a result, 5-15% of patients resected for presumed PHC have benign disease. Molecular imaging combined with cancer biomarker-specific imaging agents could serve as a novel diagnostic tool. Integrin ανβ6 is a cell surface receptor that is highly upregulated in pancreaticobiliary malignancies. We have developed imaging agents selectively binding integrin ανβ6 for both (preoperative)PET and (intraoperative)fluorescent imaging. We aimed to evaluate the expression of integrin ανβ6 in PHC and in benign disease mimicking PHC using immunohistochemistry in a pilot study. Materials and Methods: Patients with a tumour suspect for PHC who underwent resection at the Amsterdam UMC between 2000 and 2015 were evaluated and twenty patients were selected based on their pathology records and surgical specimens. Of these, ten patients had pathologically proven PHC and ten patients had benign disease mimicking PHC (IgG4, PSC, cholangitis). Formalin fixed tissue sections were immunohistochemically stained for integrin ανβ6 to investigate expression levels and patterns of expression. Results: Immunohistochemical staining for integrin ανβ6 showed membranous expression in all ten PHC samples, with intensity varying between samples and patients. The pre-existent peribiliary glands showed low-intensity integrin ανβ6 expressiong in a small number of cells. Six out of ten benign samples showed no expression of integrin ανβ6. In four benign samples, low-intensity staining of bile ducts was occasionally observed in cases with dense inflammatory infiltrates. Overall, expression levels were higher in PHC samples, compared to benign samples(Figure 1). Conclusion: Integrin ανβ6 could potentially serve as a target to differentiate PHC from benign disease mimicking PHC. These findings need to be validated in larger series of patients.