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ASPM Is a Novel Marker for Vascular Invasion, Early Recurrence, and Poor Prognosis of Hepatocellular Carcinoma

Authors' Affiliations: ¹ Graduate Institute of Pathology, College of Medicine; ² College of Public Health, National Taiwan University; ³ Department of Pathology and ⁴ National Center of Excellence for General Clinical Trial and Research, National Taiwan University Hospital; and ⁵ Department of General Education, National Taipei College of Nursing, Taipei, Taiwan, Republic of China

Requests for reprints: Hey-Chi Hsu, Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China. Phone: 886-2-23123456, ext. 5455; Fax: 886-2-23410876; E-mail: heychi{at}ntu.edu.tw.

Purpose: Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocelllular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis.

Experimental Design: 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 -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 -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).

Conclusion: 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.