Zhao Ying-fang, Shen Shu-ping, Jiang Jian-ying, Geng Hong, Guo Jian-guo, Xie Li-ping
Department of Pathology, the First Affiliated Hospital, Baotou Medical College, Baotou 014010, China.
Zhonghua Bing Li Xue Za Zhi. 2010 Jun;39(6):377-81.
(1) To investigate the promoter methylation status of gene p16(INK4a) and gene RB in breast carcinoma and the adjacent non-neoplastic hyperplastic epithelial tissue. (2) To study the correlation of p16(INK4a) gene expression at protein level with the abnormal gene methylation, the clinical manifestation and the pathological parameters.
Methylation status of promoters of p16(INK4a) gene and RB gene was detected by using methylation specific PCR in 46 cases of breast cancer, 22 cases of the adjacent non-neoplastic hyperplastic epithelium tissue and 7 cases of normal breast tissue. In addition, the p16(INK4a) gene protein expression level was also detected using immunohistochemical technique(SP method) in 46 cases of breast cancer and 22 cases of the adjacent hyperplastic epithelial tissue.
The methylation rate of p16(INK4a) gene was 23.9% (11/46) in breast cancer, 18.2% (4/22) in the adjacent non-neoplastic hyperplastic epithelial tissue and 1/7 in normal breast tissue, respectively. The methylation rate of RB gene was relatively low, which was 10.8% (5/46), 9.1% (2/22) and 0(0/7) in the above 3 groups, respectively. Methylation rate of p16(INK4a) gene and RB gene was not significantly different among the breast cancer, the adjacent non-neoplastic hyperplastic tissue and the normal tissues (P > 0.05). However, the methylation status of p16(INK4a) gene was closely correlated with its protein expression level and the negative ER expression result of the breast cancer (P < 0.05), but not correlated with the size of the cancer, differentiation status, lymph node metastasis, and age. The methylation status of RB gene was correlated with lymph node metastasis, but not with the size, the differentiation status, ER expression of the breast cancer and the age of the patients.
The abnormal methylation of p16(INK4a) gene may not play a significant role in the early stage of breast cancinogenesis, but may play a role of in the progression of the cancer. RB gene methylation may also be a indicator in choice to identify the progression and prognosis of breast cancer.
（1）研究乳腺癌及癌旁非肿瘤性增生上皮组织中p16（INK4a）基因和RB基因的启动子甲基化状态。（2）探讨p16（INK4a）基因蛋白水平表达与基因异常甲基化、临床表现及病理参数之间的相关性。
采用甲基化特异性PCR检测46例乳腺癌、22例癌旁非肿瘤性增生上皮组织及7例正常乳腺组织中p16（INK4a）基因和RB基因启动子的甲基化状态。另外，采用免疫组化技术（SP法）检测46例乳腺癌及22例癌旁增生上皮组织中p16（INK4a）基因蛋白表达水平。
p16（INK4a）基因甲基化率在乳腺癌中为23.9%（11/46），在癌旁非肿瘤性增生上皮组织中为18.2%（4/22），在正常乳腺组织中为1/7。RB基因甲基化率相对较低，上述3组分别为10.8%（5/46）、9.1%（2/22）和0（0/7）。p16（INK4a）基因和RB基因甲基化率在乳腺癌、癌旁非肿瘤性增生组织及正常组织之间差异无统计学意义（P＞0.05）。然而，p16（INK4a）基因甲基化状态与其蛋白表达水平及乳腺癌雌激素受体（ER）阴性表达结果密切相关（P＜0.05），但与肿瘤大小、分化程度、淋巴结转移及年龄无关。RB基因甲基化状态与淋巴结转移相关，但与乳腺癌的大小、分化程度、ER表达及患者年龄无关。
p16（INK4a）基因异常甲基化在乳腺癌发生早期可能不起重要作用，但可能在肿瘤进展过程中发挥作用。RB基因甲基化也可能是判断乳腺癌进展及预后的一个指标。
