Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses

Ryo Morisue, Motohiro Kojima, Toshihiro Suzuki, Tetsuya Nakatsura, Hidenori Ojima, Reiko Watanabe, Motokazu Sugimoto, Shin Kobayashi, Shinichiro Takahashi, Masaru Konishi, Genichiro Ishii, Naoto Gotohda, Toshiyoshi Fujiwara, Atsushi Ochiai

Research output: Contribution to journalArticlepeer-review

Abstract

Sarcomatoid hepatocellular carcinoma (SHCC), which was a rare histological subtype of hepatocellular carcinoma (HCC), is currently subclassified as poorly differentiated HCC because of insufficient evidence to define SHCC as a subtype of HCC. We aimed to assess the feasibility of classifying SHCC as a histological subtype of HCC by comprehensively identifying novel and distinct characteristics of SHCC compared to ordinary HCC (OHCC). Fifteen SHCCs (1.4%) defined as HCC with at least a 10% sarcomatous component, 15 randomly disease-stage-matched OHCCs and 163 consecutive OHCCs were extracted from 1106 HCCs in the Pathology Database (1997-2019) of our hospital. SHCC patients showed poor prognosis, and the tumors could be histologically subclassified into the pleomorphic, spindle and giant cell types according to the subtype of carcinomas with sarcomatoid or undifferentiated morphology in other organs. The transcriptomic analysis revealed distinct characteristics of SHCC featuring the upregulation of genes associated with epithelial-to-mesenchymal transition and inflammatory responses. The fluorescent multiplex immunohistochemistry results revealed prominent programmed death-ligand 1 (PD-L1) expression on sarcomatoid tumor cells and higher infiltration of CD4+ and CD8+ T cells in SHCCs compared to OHCCs. The density of CD8+ T cells in the nonsarcomatous component of SHCCs was also higher than that in OHCCs. In conclusion, the comprehensive analyses in our study demonstrated that SHCC is distinct from OHCC in terms of clinicopathologic, transcriptomic and immunologic characteristics. Therefore, it is reasonable to consider SHCC as a histological subtype of HCC.

Original languageEnglish
Pages (from-to)546-560
Number of pages15
JournalInternational Journal of Cancer
Volume149
Issue number3
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • epithelial-to-mesenchymal transition
  • hepatocellular carcinoma
  • programmed death-ligand 1
  • sarcomatous change
  • tumor immune microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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