title: ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma.
abstract: OBJECTIVE
  Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocellular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis.
  
  
  METHODS
  We used reverse transcription-PCR assays to measure the ASPM mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features.
  
  
  RESULTS
  ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high alpha-fetoprotein (P = 1 x 10(-8)), high-grade (grade II-IV) HCC (P = 2 x 10(-6)), high-stage (stage IIIA-IV) HCC (P = 1 x 10(-8)), and importantly ETR (P = 1 x 10(-8)). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high alpha-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 x 10(-8)), whereas ASPM overexpression (odds ratio, 6.49; P = 1 x 10(-8)) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 x 10(-8)) and non-p53-mutated HCC (P = 1 x 10(-8) and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P = 0.008).
  
  
  CONCLUSIONS
  ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shih-Yeh
authors.initials: SY
authors.lastname: Lin
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Pan
authors.forename: Shu-Hsiang
authors.initials: SH
authors.lastname: Liu
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Fu-Chang
authors.initials: FC
authors.lastname: Hu
authors.forename: Shian-Yang
authors.initials: SY
authors.lastname: Peng
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Lai
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000368:Aged; D001808:Blood Vessels / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53