Andrea Ruzzenente1, Matteo Fassan2,3, Simone Conci1, Michele Simbolo2,3, Rita T Lawlor2,3, Corrado Pedrazzani1, Paola Capelli3, Mirko D'Onofrio4, Calogero Iacono1, Aldo Scarpa2,3, Alfredo Guglielmi5. 1. Department of Surgery, General and Hepatobiliary Surgery, University Hospital G.B. Rossi, University of Verona, Verona, Italy. 2. ARC-Net Research Center, University Hospital G.B. Rossi, University of Verona, Verona, Italy. 3. Department of Pathology and Diagnostics, University Hospital G.B. Rossi, University of Verona, Verona, Italy. 4. Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy. 5. Department of Surgery, General and Hepatobiliary Surgery, University Hospital G.B. Rossi, University of Verona, Verona, Italy. alfredo.guglielmi@univr.it.
Abstract
BACKGROUND: Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. METHODS: Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. RESULTS: The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK, IDH1, and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC (p < 0.001, p = 0.043, and p = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC (p = 0.049). The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively). CONCLUSIONS: Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.
BACKGROUND:Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. METHODS: Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. RESULTS: The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK, IDH1, and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC (p < 0.001, p = 0.043, and p = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC (p = 0.049). The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively). CONCLUSIONS: Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.
Authors: Farshad Farshidfar; Siyuan Zheng; Marie-Claude Gingras; Yulia Newton; Juliann Shih; A Gordon Robertson; Toshinori Hinoue; Katherine A Hoadley; Ewan A Gibb; Jason Roszik; Kyle R Covington; Chia-Chin Wu; Eve Shinbrot; Nicolas Stransky; Apurva Hegde; Ju Dong Yang; Ed Reznik; Sara Sadeghi; Chandra Sekhar Pedamallu; Akinyemi I Ojesina; Julian M Hess; J Todd Auman; Suhn K Rhie; Reanne Bowlby; Mitesh J Borad; Andrew X Zhu; Josh M Stuart; Chris Sander; Rehan Akbani; Andrew D Cherniack; Vikram Deshpande; Taofic Mounajjed; Wai Chin Foo; Michael S Torbenson; David E Kleiner; Peter W Laird; David A Wheeler; Autumn J McRee; Oliver F Bathe; Jesper B Andersen; Nabeel Bardeesy; Lewis R Roberts; Lawrence N Kwong Journal: Cell Rep Date: 2017-06-27 Impact factor: 9.423
Authors: Maeve A Lowery; Howard A Burris; Filip Janku; Rachna T Shroff; James M Cleary; Nilofer S Azad; Lipika Goyal; Elizabeth A Maher; Lia Gore; Antoine Hollebecque; Muralidhar Beeram; Jonathan C Trent; Liewen Jiang; Bin Fan; Elia Aguado-Fraile; Sung Choe; Bin Wu; Camelia Gliser; Samuel V Agresta; Shuchi S Pandya; Andrew X Zhu; Ghassan K Abou-Alfa Journal: Lancet Gastroenterol Hepatol Date: 2019-07-09