子宫内膜癌组织中PTEN基因突变及蛋白表达的检测

Detection of Mutation and Protein Expression of PTEN Gene in Endometrial Carcinoma

背景与目的:肿瘤抑制基因———第10染色体同源丢失性磷酸酶-张力蛋白基因(phosphataseandtensinhomologdeletedonchromosometen,PTEN)被称为子宫内膜的看家基因。但有关PTEN基因在子宫内膜癌发生发展中的确切作用尚不清楚。本研究旨在检测子宫内膜癌组织中PTEN基因的突变及蛋白表达情况。方法:应用聚合酶链反应-单链构象多态性分析(polymerasechainreaction-singlestranconformationpolymorphism,PCR-SSCP)和DNA序列分析法,检测52例子宫内膜癌组织和10例正常子宫内膜组织中PTEN基因第5和第8外显子的突变;免疫组织化学法检测PTEN蛋白的表达,并结合临床病理特征进行分析。结果:子宫内膜癌组织的PTEN基因突变率和蛋白缺失率分别为25%和60%,高于正常子宫内膜组织(0%),差异有显著性(P<0.05)。病理学分级为G1、G2及肌层浸润深度<1/2的组织的PTEN基因突变率高于病理学分级为G3及肌层浸润深度≥1/2者,而病理学分级为G1、G2组织的PTEN蛋白表达缺失率低于病理学分级为G3者,差异有显著性(P<0.05)。PTEN基因突变率和蛋白表达缺失率在子宫内膜样腺癌和其它组织类型之间比较,差异有显著性(P<0.05),而在不同手术分期之间差异无显著性(P>0.05)。

BACKGROUND &OBJECTIVE: PTEN (phosphatase and tensin homolog deleted on chromosome ten), a novel tumor suppressor gene identified recently, is calle d the house-keeping gene of endometrium. However, little is known about its pre cise role in genesis and development of endometrial carcinoma. In the present st udy, the mutation and protein expression of PTEN gene were investigated to seek the clinical significance. METHODS: Fifty-two endometrial carcinoma samples and 10 normal endometrial tissues were collected. The mutations of exon 5 and exon 8 of PTEN gene were examined by polymerase chain reaction-single strand conform ation polymorphism (PCR-SSCP) and DNA sequencing analysis. The expression of PT EN protein was evaluated by immunohistochemistry method. The results associated with clinical pathological features were analyzed. RESULTS: In endometrial carci nomas, the rates of mutation and protein expression deletion of PTEN were 25%an d 60%, respectively, which were significantly higher than that of normal endome trium (0%) (P< 0.05). The samples at pathological G1 and G2 and depth of myomet rial invasion less than 1/2 demonstrated higher mutation rate than that of G3 an d depth of myometrial invasion more than or equal to 1/2 (P< 0.05). In contrast, the rate of protein expression deletion of G1 and G2 was significantly lower th an that of G3 (P< 0.05). Both mutation and protein expression deletion showed st atistical differences between endometrioid adenocarcinoma and other types of end ometrial carcinomas (P< 0.05), but no significant difference was found at differ ent surgical-pathological stage (P >0.05). CONCLUSION: Mutation and positive pr otein expression of PTEN occurred more frequently in the endometrial carcinoma c ases with low pathological stages.