2006 Fiscal Year Final Research Report Summary
Heparanase expression correlates with angiogenesis and predicts tumor metastasis in endometrial cancer.
| Project/Area Number |
17591723
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | University of the Ryukyus (2006)
Niigata University (2005) |
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Principal Investigator |
AOKI Yoichi Univ. of the Ryukyus, Faculty of Med., Dept Ob/Gyn, Professor, 医学部, 教授 (40231774)
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| Project Period (FY) |
2005 – 2006
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| Keywords | heparanase / RT-PCR / anti-heparanase antibody / endometrial cancer / angiogenesis / imunohistochemical staining |
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| Research Abstract |
The human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Fifty-two endometrial cancers were obtained from previously untreated patients (median age, 56 years, range, 35-80 years). The expression of heparanase mRNA was evaluated using a semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining (IHC) with anti-heparanase polyclonal antibody. This antibody was raised by immunizing a rabbit with a peptide containing the amino acid residues from 238 to 250 of the Heparanase. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one factor ANOVA test, and Spearman' s test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 26 of 52 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p=0.0075), the presence of lymph-vascular space involvement (LVSI) (p=0.0041), lymph node metastasis (LNM) (p=0.0049), and histological tumor grade (p=0. 003). IHC showed that the heparanase was expressed in 23 of the 52 (44. 2%) samples, which was significantly related to LVSI (p=0.0028), depth of myometrial invasion (p=0.0026), and histological tumor grade (p=0.0135). Microvessel density was also associated with FIGO stage IIIc (p=0.027), LVSI (p=0.001), LNM (p=0.038), ovarian metastasis (p=0.03) and histological tumor grade (p=0.003). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2=0.475, p=0.0001). These results suggest that the expression of heparanase can promote tumor angiogenesis and develop metastasis in endometrial cancer.
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