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01-05-2016 | Hepatobiliary Tumors

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

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

Published in: Annals of Surgical Oncology | Issue 5/2016

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.

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Title: Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients
Authors: Andrea Ruzzenente, MD, PhD
Matteo Fassan, MD, PhD
Simone Conci, MD
Michele Simbolo, MD
Rita T. Lawlor, MD
Corrado Pedrazzani, MD
Paola Capelli, MD
Mirko D’Onofrio, MD
Calogero Iacono, MD
Aldo Scarpa, MD
Alfredo Guglielmi, MD
Publication date: 01-05-2016
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 5/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-015-5046-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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