【摘要】 目的 :通过研究磷脂酰肌醇激酶-3催化亚基α基因(PIK3CA)突变和类脂磷酸酶(PTEN)蛋白表达缺失与临床病理指标间的关系,进一步探讨其在乳腺癌发生、发展中的意义。方法:收集86例经病理确诊的乳腺癌石蜡标本,检测PIK3CA基因第9、20外显子的突变以及PTEN的蛋白表达。分析上述两者之间的关系,以及与乳腺癌肿块大小、雌/孕激素受体(ER/PR)状态、表皮生长因子受体-2(Her-2)状态、淋巴结转移之间的关系。结果:PIK3CA基因突变为28例(占32.6%),突变与肿瘤大小无相关性(x2=0.104,P=0.747)。在ER/PR阳性、Her-2阳性、淋巴结转移阳性患者中PIK3CA突变发生率高,对比阴性者差异有统计学意义(x2=9.022,P=0.003;x2=5.752,P=0.016;x2=4.599,P=0.032)。在淋巴结阳性患者中,20号外显子的突变率为64.7%(11/17),与淋巴结阴性患者比差异有统计学意义(x2=4.809,P=0.028)。PTEN表达阴性者38例(占44.2%),而在PTEN阳性表达的48例中,ER/PR阳性患者明显高于ER/PR阴性患者(x2=17.667,P=0.000);有淋巴结转移者明显低于无淋巴结转移者(x2=12.884,P=0.000)。PTEN表达缺失与肿瘤大小、Her-2状态无关。结论:PIK3CA基因的突变及PTEN蛋白表达缺失是乳腺癌中常见的事件,PIK3CA突变多发生于激素受体阳性患者中,而PTEN表达缺失多发生于激素受体阴性患者。这些改变表明不同基因型肿瘤其发生发展的不同途径,同时提示不良的临床预后。更多还原

【Abstract】 Objective: To further explore the significance of its relationship in carcino-genesis and development of breast cancer through the research on the relationship among PIK3CA mutation,PTEN loss and the clinical pathological marker.Methods: Exons 9 and 20 of the PIK3CA gene were analyzed in 86 breast tumors,and mutations were detected by single-stranded confor-mational analysis followed by sequencing.The expression of PTEN was evaluated with immunohis-tochemistry in 86 tumors.Results: PIK3CA mutations were found in 28(32.6%) of the tumors and associated with estrogen and/or progesterone receptors+(ER/PR+),lymph node metastasis,and ERBB2 overexpression(x2=9.022,P =0.003,x2=5.752,P =0.016,x2=4.599,P =0.032).PIK3CA exon 20 mu-tation was significant in the patients with lymph node metastasis(x2=4.809,P =0.028),was an independent risk factor for poor prognosis.PTEN was negative in 38(44.2%) of the cases and PTEN loss was associated with estrogen and/or progesterone receptors+(ER/PR+) and lymph node metastasis(x2=17.667,P =0.000,x2=12.884,P =0.000).Conclusion: PIK3CA mutations and PTEN loss are common alterations in breast cancer.The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution.PIK3CA mutations and PTEN loss are associated with poor similar prognostic factors.更多还原