乳腺癌中PIK3CA基因突变与HER2表达及其基因扩增的关系

摘要

目的 探讨乳腺癌中PIK3CA基因突变与HER2蛋白表达和基因扩增之间的关系.方法 收集134例乳腺癌组织,采用免疫组化EnVision两步法检测HER2蛋白表达,采用FISH法检测HER2基因扩增,运用突变富集液相芯片法检测PIK3CA基因第9、20号外显子的突变状况,分析PIK3CA基因突变与HER2蛋白表达和基因扩增之间的关系.结果 134例乳腺癌组织中,49例检测到PIK3CA基因突变,突变率为36.6%,其中第9号外显子突变者16例(32.7%),20号外显子突变者33例(67.3%),50例(37.3%)检测有HER2基因扩增.在50例HER2基因扩增的病例中12例有PIK3CA基因突变(24.0%),84例无HER2基因扩增的病例中37例有PIK3CA基因突变(44.0%).有HER2基因扩增的乳腺癌PIK3CA基因突变率较无HER2基因扩增的乳腺癌低,差异具有统计学意义(χ2=5.431,P=0.020).PIK3CA基因突变与HER2蛋白表达的关系受HER2阳性定义标准的影响,不具有确定性.分别按乳腺癌HER2检测指南(2006版)、乳腺癌HER2检测指南(2009版)及2012年WHO乳腺肿瘤分类标准对入组病例进行分组分析,其中按2006版标准,PIK3CA基因突变率在HER2蛋白表达组间无差异(χ2=2.751,P=0.253);按2009版标准,PIK3CA基因突变率在HER2蛋白表达3+与非3+组间有差异(χ2=5.478,P=0.019);按2012版标准,PIK3CA基因突变率在HER2阳性与阴性组间有差异(χ2=4.286,P=0.038).结论 PIK3CA基因突变率在FISH检测的HER2基因扩增阳性与阴性之间有差异,HER2基因扩增的乳腺癌PIK3CA基因突变率低,与HER2蛋白表达的关系与阳性判断标准有关.%Purpose To study the relationship between PIK3CA gene mutation and HER2 gene amplification and protein expression in breast cancer. Methods HER2 gene amplification and protein expression were examined in 134 breast cancer by FISH and IHC. Mutations of exon 9 and 20 of PIK3CA gene were examined by mutant-enrich liquid chip method. Results PIK3CA gene mutation was i-dentified in 36. 6% ( 49/134 ) of patients with breast cancer, 16 occurred in exon 9 ( 32. 7% ) and 33 in exon 20 ( 67. 3% ). HER2 gene amplification was identified in 50 patients ( 37. 3% ). The frequency of PIK3CA gene mutation and HER2 gene amplification was nearly the same, however, only 12 patients simultaneously had PIK3CA gene mutation and HER2 gene amplification. The mutation rate was significantly higher in the patients without HER2 amplification compared with the patients with HER2 amplification ( 44. 0% vs 24. 0% , X2=5. 431, P =0. 020 ). The correlation of PIK3CA gene mutations and HER2 protein expression was not consistent based on the different evaluation systems. PIK3CA gene mutations and HER2 protein expression were analyzed based on the standard of guideline of HER2 detection in breast ( 2006 ), PIK3CA gene mutations was independent of HER2 status( X2= 2. 751, P = 0. 253 ). If based on the standard of guideline of HER2 detection in breast ( 2009 ) and WHO classification of tumors of the breast-2012, PIK3CA mutations was associated with negative HER2 status ( X2 = 5. 478, P = 0. 019 and X2 = 4. 286, P = 0. 038 ). Conclusion PIK3CA gene mutation is negatively correlated with HER2 amplification in breast cancer, however, the relationship of PIK3CA gene mutation with HER2 protein expression is associated with the evaluation system of HER2 expression.