乳腺癌p16基因甲基化及与蛋白表达的关系

目的:探讨散发性乳腺癌中p16基因异常甲基化状况及其与蛋白表达的关系,进而研究散发性乳腺癌中p16基因异常的表遗传学作用。方法:用甲基化特异PCR(MSP)和SP法研究68例乳腺癌组织及相应癌旁正常组织中p16基因启动子甲基化状况及蛋白表达情况。结果:p16基因在68例散发性乳腺癌组织中的甲基化率为29%,且其甲基化与肿瘤组织分型、患者居住地及淋巴结转移相关(P<0.05),而与肿瘤患者绝经与否及组织分级无关(P>0.05);P16蛋白在所有肿瘤标本中的表达下降率为51%,在相应癌旁组织中均呈阳性表达,二者有显著性差异(P<0.05),P16蛋白表达下降与肿瘤患者淋巴结转移及患者居住地明显相关(P<0.05),与患者绝经、组织分级和分型无关(P>0.05);在20例p16甲基化的癌组织标本中,P16蛋白表达下降率(95%),显著高于48例未发生甲基化的乳腺癌标本下降率(33%),两者有显著性差异(P<0.05),乳腺癌患者组织p16基因甲基化检出率与P16蛋白表达下降率具有良好的一致性(Kappa=0.506),而p16未发生甲基化的正常乳腺组织和乳腺良性病变组织其蛋白均呈阳性表达。结论:在散发性乳腺癌中p16启动子甲基化改变会明显降低P16蛋白表达,p16基因启动子甲基化是其蛋白表达下降的重要原因,这种机制更倾向于农村乳腺癌患者。

Methylation and Expression of p16 Gene in Sporadic Breast Cancer and Their Relationship

Objective To investigate the methylation status of p16 gene and the level of P16 protein expression,so as to explore epigenetics role of aberrant p16 gene in sporadic breast cancer.Methods The hypermethylation status of p16 promoter regions and expression of P16 protein were determined with methylation-specific PCR（MSP） and SP staining in 68 cases of breast carcinoma tissues and homologous adjacent normal tissues.Results The methylation rate of p16 gene was 29% in 68 cases of breast carcinoma tissues and the methylation was significantly related with histological type,area,lymphatic metastasis（P0.05）,but had no significant relationship with menopausal status and histological stage（P0.05）.The decline rate of P16 protein expression was 51% in all carcinoma tissues,while the expression of P16 protein in adjacent normal tissues were positive and which was significant difference from that of the carcinoma tissues（P0.05）.The decrease of P16 protein expression was significantly related with lymphatic metastasis and area（P0.05）,but had no significant relationship with menopausal status,histological stage,histological type（P0.05）.The decline rate of P16 expression in 20 cases of P16 methylated tissues（95%） was significant higher than that in 48 cases of unmethylated tissues（33%）（P0.05）.There was a significant concordance between p16 methylation and its decline expression（Kappa=0.506）.Conclusion The methylation change of p16 gene promoter may play an important role in the declined expression of P16 protein in sporadic breast cancer,which was inclined to rural residents.