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Heparanase expression correlates with angiogenesis and predicts tumor metastasis in endometrial cancer.

乙酰肝素酶表达与血管生成相关并预测子宫内膜癌的肿瘤转移。

基本信息

批准号：
17591723
负责人：
AOKI Yoichi
金额：
$ 2.18万
依托单位：
University of the Ryukyus (2006)Niigata University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

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.

人乙酰肝素酶已被证明在肿瘤进展、转移扩散和肿瘤血管生成中起作用。本研究的目的是评估乙酰肝素酶在子宫内膜癌中的表达及其与新生血管和临床病理因素的关系。52例子宫内膜癌患者来自未经治疗的患者(中位年龄56岁，范围35-80岁)。采用半定量逆转录聚合酶链式反应和抗肝素酶多克隆抗体免疫组织化学(IHC)法检测肝素酶mRNA的表达。这种抗体是用含有乙酰肝素酶238到250个氨基酸残基的多肽免疫兔子而产生的。微血管计数法检测肿瘤血管生成情况。采用Mann-Whitney U检验、单因素方差分析和S检验分析肝素酶表达与微血管密度、临床病理参数之间的关系。在52例子宫内膜癌中，有26例(50%)乙酰肝素酶基因表达阳性，且与FIGO分期(p=0.0075)、有无淋巴管侵犯(p=0.0041)、有无淋巴结转移(p=0.0049)和组织学分级(p=0)显著相关。003)。免疫组化结果显示，肝素酶在52例中有23例(44例)有表达。2%)，与LVSI(p=0.0028)、肌层侵犯深度(p=0.0026)和组织学分级(p=0.0135)显著相关。微血管密度与FIGO分期(p=0.027)、左心室指数(p=0.001)、淋巴结转移(p=0.038)、卵巢转移(p=0.03)和组织学分级(p=0.003)有关。此外，肝素酶的表达与微血管密度呈显著正相关(R2=0.475，p=0.0001)。提示乙酰肝素酶在子宫内膜癌中的表达可促进肿瘤血管生成，促进肿瘤转移。