Practical guidelines for molecular testing of cholangiocarcinoma in clinical practice: Italian experts’ position paper
Matteo Fassan, Valentina Angerilli, Nicola Normanno, Giancarlo Pruneri, Antonio Marchetti, Federica Grillo, Giuseppe Tonini, Aldo Scarpa, Lorenza Rimassa
Abstract
Biliary tract cancers (BTCs) represent a spectrum of malignancies associated with a dismal prognosis. Recent genomic profiling studies have provided a deeper understanding of the complex and heterogenous molecular landscape of BTCs, identifying several actionable genetic alterations, and expanding treatment options. Due to the high number and complexity of genetic alterations which require testing, next-generation sequencing (NGS) is currently the preferred approach over conventional methods (i.e., immunohistochemistry, fluorescence in-situ hybridization and PCR) for molecular profiling of BTCs and should be performed upfront in all BTC patients. However, BTC sampling often yields low tumor cellularity tissue, hampering NGS analysis. Future perspectives to overcome this obstacle include liquid biopsy and optimization of biopsy protocols. In this position paper, the authors discuss the current histopathologic, molecular, and therapeutic landscape of BTCs, provide a critical overview of the available testing methods for molecular diagnostics, and propose a practical diagnostic algorithm for molecular testing of BTC samples. • Several actionable genetic alterations can be found biliary tract cancers (BTCs). • Next-Generation Sequencing is the gold standard for molecular testing in BTCs. • Scarce tumor tissue causes high rate of failure in molecular profiling. • The dialog among gastroenterologists, radiologists, pathologist and oncologists is crucial.