Distinction of intrahepatic metastasis from multi centric carcinogenesis in multifocal hepatocellular carcinoma using molecular alterations

被引:25
作者
Chianchiano, Peter [1 ]
Pezhouh, Maryam Kherad [1 ]
Kim, Amy [2 ]
Luchini, Claudio [3 ]
Cameron, Andrew [4 ]
Weiss, Matthew J. [4 ]
He, Jin [4 ]
Voltaggio, Lysandra [1 ]
Oshima, Kiyoko [1 ]
Anders, Robert A. [1 ]
Wood, Laura D. [1 ,5 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21231 USA
[3] Univ Verona, Sect Pathol, Dept Diagnost & Publ Hlth, I-37134 Verona, Italy
[4] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21231 USA
[5] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
基金
美国国家卫生研究院;
关键词
Multifocal hepatocellular carcinoma; Multicentric carcinogenesis; Intrahepatic metastasis; Sanger sequencing; Next-generation sequencing; CLONAL ORIGIN; SOMATIC MUTATIONS; RECURRENCE; RESECTION; PROMOTER; TUMORS;
D O I
10.1016/j.humpath.2017.11.011
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Patients with hepatocellular carcinoma (HCC) frequently have multiple anatomically distinct tumors. In these patients, multifocal HCC could represent intrahepatic metastases (IMs) of a single cancer or multidentric carcinogenesis (MC) with multiple independent neoplasms. To determine the frequency and clinical implications of these 2 possibilities, we performed histological and molecular analysis of 70 anatomically distinct HCCs from 24 patients. We assayed mutations in the TERT promoter region by Sanger sequencing and used next-generation sequencing to analyze the entire coding regions of 7 well-characterized HCC driver genes based on shared or discordant mutations in these genes, we classified the HCCs in each patient as IM, MC, or indeterminate. Mutations in the TERT promoter were the most common alteration in our cohort, present in 71% of tumors analyzed. Mutations in the remaining genes occurred in less than 20% of analyzed tumors. We were able to determine the relatedness in 58% of the patients analyzed: MC occurred in 41% of patients, with 33% with exclusively MC and 8% with both MC and IM. IM occurred exclusively in 17% of patients, whereas the remainder were indeterminate. This study highlights the utility of molecular analyses to determine relatedness in multifocal HCC; however, targeted sequencing can only resolve this distinction in approximately 60% of patients with multifocal HCC. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:127 / 134
页数:8
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