title: Gene expression signature of the gross morphology in hepatocellular carcinoma.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tokyo, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Murakata
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yasen
authors.forename: Norio
authors.initials: N
authors.lastname: Noguchi
authors.forename: Takumi
authors.initials: T
authors.lastname: Irie
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kudo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate