Background
Gross vascular invasion is a well-established prognostic indicator in hepatocellular
carcinoma (HCC), but the biological significance of microscopic invasion remains unclear.
Methods
Curatively resected primary HCCs were classified retrospectively into 3 groups: HCCs
without vascular invasion (V0), HCCs with microvascular invasion (V1), and HCCs with
macrovascular invasion (V2). Microarray profiling of patients with V0, V1, and V2
using Jonckheere-Terpstra (JT) tests and Wilcoxon rank sum tests was performed.
Results
Distinct patterns of gene expression were demonstrated between V0 and V2 groups; less
(L) and highly (H) invasive phenotypes, respectively. It is noteworthy that 2 dendrograms
by the hierarchical clustering provided exactly the same assignment results for V1
cases that were thus separated into L and H gene-expression phenotypes. Marked differences
were found in overall (P < .001) and tumor-free survival (P < .001) between L and H gene-expression phenotypes. Multivariate analyses indicated
that the phenotypes of the patterns of gene expression, rather than the clinicopathologic
markers of vascular invasion, were independent predictors of tumor recurrence (P = .031). Using the gene-expression patterns identified by both JT and Wilcoxon rank
sum test analyses, other V1 cases validated these differences in tumor-free survivals
between gene-expression phenotypes within the group (P = .039).
Conclusion
Gene profiling suggested that microvascular invasiveness consisted of a classable
mixture of 2 distinct phenotypes. Thus, gene-array analyses may have clinical benefit,
because they may in fact be more predictive than other clinical factors.
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Article info
Publication history
Published online: November 30, 2009
Accepted:
September 29,
2009
Footnotes
Supported by Special Coordination Funds for Promoting Science & Technology (Japan Science & Technology Agency) and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. S.T. is a recipient of the Japan Cancer Society Incitement Award and the Japan Society for the Promotion of Science Prize.
Identification
Copyright
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
