Details

Autor(en) / Beteiligte

• Ruzzenente, Andrea
• Fassan, Matteo
• Conci, Simone
• Simbolo, Michele
• Lawlor, Rita T.
• Pedrazzani, Corrado
• Capelli, Paola
• D’Onofrio, Mirko
• Iacono, Calogero
• Scarpa, Aldo
• Guglielmi, Alfredo

Titel

Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients

Ist Teil von

• Annals of surgical oncology, 2016-05, Vol.23 (5), p.1699-1707

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.