子宫内膜癌组织中垂体肿瘤转化基因PTTG的表达及其意义

Expression of pituitary tumor-transforming gene in endometrial carcinoma

目的 检测子宫内膜癌组织中垂体肿瘤转化基因PTTG的表达,并分析其与碱性成纤维细胞生长因子(bFGF)蛋白表达和微血管密度(MVD)计数的相关性,探讨其在子宫内膜癌发生、发展中的作用。方法 采用RT-PCR技术,检测50例子宫内膜癌组织中PTTG mRNA的表达,并进行半定量分析;应用免疫组化链霉菌抗生物素蛋白-过氧化酶连接(SP)法,检测PTTG和bFGF蛋白的表达,CD34标记血管内皮细胞并计数肿瘤间质MVD;结合临床病理特征、bFGF蛋白及MVD计数进行分析。另选择15例增生性子宫内膜和12例正常子宫内膜组织作为对照。结果 子宫内膜癌组织中PTTG基因呈过度表达,内膜癌组织中PTTG mRNA的阳性表达率及平均表达水平(分别为96％,0.84±0.08)显著高于增生性子宫内膜(分别为60％,0.78±0.06)及正常子宫内膜组织(分别为33％,0.48±0.12),3组间分别比较,差异均有极显著性(P<0.01);内膜癌组织中PTTG蛋白的阳性表达率(70％)明显高于增生性子宫内膜(40％)及正常子宫内膜组织(17％),3组间分别比较,差异也均有极显著性(P<0.01);PTTG基因的表达与手术病理分期、淋巴结转移及肌层浸润有明显相关性(P<0.05),且其在子宫内膜样腺癌组织中的表达显著高于其他类型的内膜癌组织(P<0.05);PTTG基因的表达与年龄及病理分级无关(P>0.05)。

Objective To study the expression of pituitary tumor-transforming gene (PTTG) and its relationship with the expression of basic fibroblast growth factor ( bFGF) protein and microvessel density (MVD) in endometrial carcinoma. Methods Expressions of PTTG mRNA and protein were assessed by semi-quantitive RT-PCR and immunohistochemistry methods respectively in 50 cases of endometrial carcinomas, 15 cases of hyperplasia endometria and 12 cases of normal endometrial tissue. Expressions of bFGF protein were detected by immunohistochemistry. Microvessels were highlighted by staining endothelial cells with CD34 antigen, and MVDs were counted Results The expression rate and average quantity of PTTG mRNA were detected in a significantly greater proportion endometrial carcinomas (96% ,0. 84 ±0. 08) than in hyperplasia endometria (60% ,0.78 ± 0.06) and normal endometrial tissue (33% ,0.48 ± 0. 12, P <0. 01 .respectively). The expression of PTTG protein in endometrial carcinomas (70% ) was significantly higher than in hyperplasia endometria (40%) and normal endometrial tissue (17%, P < 0. 01 ) . The expression of PTTG was related to surgical-pathological stage, myometrial infiltration depth, lymphatic metastasis and pathological subtype (P < 0. 05, respectively), but was irrelevant to patients' age and pathological grade (P > 0. 05, respectively). The average quantity of PTTG mRNA and expression rate of PTTG protein in tissues with bFGF protein coexpression(0. 86 ± 0.07,87%) were higher than in those without bFGF protein coexpression (0. 80 ± 0. 06, 42% , P <0. 01 .respectively). The MVD in tissues with PTTG protein expression (62 ± 18) was higher than in those without PTTG protein expression (51 ± 12, P < 0.05). Conclusions PTTG may play an important role in carcinogenesis and development of endometrial carcinoma. PTTG induces an angiogenesis through bFGF which is a key determinant step in tumor progression and metastatic spread.