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Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis
Author(s) -
Sato Tomohiro,
Yamaguchi Akio,
Goi Takanori,
Hirono Yasuo,
Takeuchi Kazuo,
Katayama Kanji,
Matsukawa Shigeru
Publication year - 2004
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20097
Subject(s) - heparanase , medicine , metastasis , colorectal cancer , angiogenesis , cancer research , cancer , immunohistochemistry , oncology , pathology
Background Heparanase is considered to play an important role in tumor invasion and hematogenous metastasis. The aim of this study was to determine the expression of heparanase in colorectal cancer to evaluate its prognostic value. Methods We analyzed heparanase mRNA derived from 130 colorectal cancer patients by reverse transcription polymerase chain reaction (PCR), compared its expression with clinicopathologic factors, and performed statistical analysis. To investigate the relationship between heparanase expression and tumor angiogenesis, 81 primary colorectal tumors were immunostained by use of a monoclonal anti‐CD34 antibody. Results Thirty three of 130 cancer tissues overexpressed heparanase. There were significant correlations between heparanase expression and serosal invasion, venous invasion, and liver metastasis. Multivariate analyzes revealed that heparanase mRNA overexpression was a significant independent risk factor for hematogenous metastasis in colorectal cancer. Among 104 patients who underwent curative resection, heparanase expression correlated with a high recurrence. The 5‐year survival rate was 84.6% for patients with heparanase negative tumors, and 47.7% for those with heparanase overexpression; these differences between two groups of patients were significant. In multivariate analysis using the Cox regression model, heparanese expression emerged as an independent prognostic indicator. Moreover, the tumor angiogenesis of heparanase‐positive tumors determined with a monoclonal anti‐CD34 antibody was significantly higher than that of heparanase‐negative tumors. Conclusions These results indicated that Heparanase expression may be an important role in invasion and hematogenous metastasis, and may be a biologic marker of prognostic significance in colorectal cancer patients. J. Surg. Oncol. 2004;87:174–181. © 2004 Wiley‐Liss, Inc.