Gene expression signature of the gross morphology in hepatocellular carcinoma

Ayano Murakata, Shinji Tanaka, Kaoru Mogushi, Mahmut Yasen, Norio Noguchi, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Shigeki Arii

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Objective: To evaluate the gene expression signature of hepatocellular carcinoma (HCC) in relation to the gross morphology. Background: Eggel's nodular type of HCC is morphologically subclassified into the single nodular (SN) type, the single nodular type with extranodular growth (SNEG), and the confluent multinodular (CM) type, but their biomolecular differences remain unclear. Methods: The clinicopathological characteristics and genome-wide gene expressions were analyzed in 275 patients with nodular-type HCC (124 SN-type, 91 SNEG-type, and 60 CM-type) who received curative hepatectomy. Results: Significantly poor prognosis was recognized in CM types in overall survival (P = 0.0020) and recurrence-free survival (P = 0.0066). Analysis of the genome-wide expression patterns revealed significant difference of CM-type HCC from either SN-or SNEG-type HCC. In particular, a stem cell marker EpCAM was dominantly expressed in CM-type HCC. Immunohistochemical studies confirmed the specific expression of EpCAM in HCC cancer cells of CM type. In multivariate analysis, the gross morphology of CM type was significantly associated with EpCAM expression (P = 0.0092), α-fetoprotein (P = 0.0424), "lens culinaris agglutinin-reactive fraction of α-fetoprotein" level (P = 0.0288), and the portal vein invasion (P = 0.0150). Furthermore, EpCAM was predictive for poor prognosis in overall and recurrence-free survivals of patients with CM-type HCC (P = 0.0082 and P = 0.0043, respectively). Conclusion: Our studies suggest that the distinct signature of gene expression is closely related to morphological progression in HCC. Especially, EpCAM might play a critical role in the aggressiveness of CM-type HCC.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalAnnals of Surgery
Issue number1
Publication statusPublished - 2011 Jan

ASJC Scopus subject areas

  • Surgery


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