Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis.
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.
Sato
Tomohiro
T
First Department of Surgery, University of Fukui, Matsuoka-cho, Yoshida-gun, Fukui, Japan.
Yamaguchi
Akio
A
Goi
Takanori
T
Hirono
Yasuo
Y
Takeuchi
Kazuo
K
Katayama
Kanji
K
Matsukawa
Shigeru
S
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D010534:Peritoneal Neoplasms / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099175:Heparanase
D005966:Glucuronidase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012333:RNA, Messenger; D000099175:Heparanase