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

已显示人乙酰肝素酶在肿瘤进展、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与新生血管和临床病理因素的相关性。52例子宫内膜癌患者来自既往未经治疗的患者（中位年龄56岁，范围35-80岁）。半定量逆转录聚合酶链反应和免疫组化染色（IHC）抗乙酰肝素酶多克隆抗体的乙酰肝素酶mRNA的表达进行了评价。该抗体通过用含有乙酰肝素酶的238 - 250位氨基酸残基的肽免疫兔子而产生。采用微血管计数评估肿瘤血管生成。采用Mann-Whitney U检验、单因素方差分析和斯皮尔曼检验确定乙酰肝素酶表达、微血管密度和临床病理参数之间的关系。在52例子宫内膜癌中，有26例（50%）检测到乙酰肝素酶mRNA的表达，并与FIGO IIIc期（p=0.0075）、淋巴管间隙受累（LVSI）（p=0.0041）、淋巴结转移（LNM）（p=0.0049）和组织学肿瘤分级（p=0.0049）显著相关。003）。免疫组化结果显示，在52个细胞中有23个表达乙酰肝素酶（44.这与LVSI（p=0.0028）、子宫肌层浸润深度（p=0.0026）和组织学肿瘤分级（p=0.0135）显著相关。微血管密度还与FIGO IIIc期（p=0.027）、LVSI（p=0.001）、LNM（p=0.038）、卵巢转移（p=0.03）和组织学肿瘤分级（p=0.003）相关。此外，我们发现乙酰肝素酶的表达和微血管密度之间有很强的正相关性（r2=0.475，p=0.0001）。这些结果表明，乙酰肝素酶的表达可以促进子宫内膜癌的肿瘤血管生成和发展转移。

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.