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

Peter Chianchiano, Maryam Kherad Pezhouh, Amy Kim, Claudio Luchini, Andrew M Cameron, Matthew J Weiss, Jin He, Lysandra Voltaggio, Kiyoko Oshima, Robert A Anders, Laura Delong Wood

Research output: Contribution to journalArticle


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 multicentric 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.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalHuman Pathology
Publication statusPublished - Feb 1 2018



  • Intrahepatic metastasis
  • Multicentric carcinogenesis
  • Multifocal hepatocellular carcinoma
  • Next-generation sequencing
  • Sanger sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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