p16INK4a蛋白可作为乳腺癌特异性分子标志

p16INK4a protein is a specific molecular biomarker of breast cancer

目的探讨p16INK4a蛋白在乳腺癌中的表达及其临床意义。方法收集2014年～2015年间手术切除的132例乳腺癌标本,采用罗氏全自动免疫组化染色仪进行免疫组织化学染色,检测ER、PR、Her-2、Ki67、CK5/6、和p16INK4a表达,并按照不同表达模式进行结果判读和分子分型,观察p16INK4在乳腺癌中的表达及其与乳腺癌免疫表型、分子亚型及临床指标的相关性。结果 132例浸润性乳腺癌中Luminal A型58例、Luminal B型32例、Her-2型21例、basal-like（BLBC）型12例、Normal-like型9例。p16INK4a蛋白表达阴性（0）、弱阳性（1＋）、阳性（2＋）和强阳性（3＋）表达样本分别占总数的5.30%（7/132）、11.36%（15/132）、30.30%（40/132）、53.03%（70/132）。按照p16INK4a表达强度,将阴性（0）和弱阳性（1＋）病例合并为阴性组（≤1＋）、将阳性（2＋）和强阳性（3＋）病例合并为阳性组（≥2＋）,p16INK4a阴性（≤1＋）表达率为16.67%（22/132）、p16INK4a阳性（≥2＋）表达率为83.33%（110/132）。按照构成比进行统计分析,发现p16INK4a蛋白的表达强度除在不同年龄分组中具有统计学差异（P〈0.05）之外,与ER、PR、Her-2及分子分型和是否存在转移之间均无统计学差异（P〉0.50）。结论 p16INK4A代偿性高表达是浸润性乳腺癌细胞周期异常的主要机制,且p16INK4A可作为浸润性乳腺癌细胞特异性的分子标志,采用IHC技术检测p16 INK4a的表达不仅为乳腺癌诊断提供了一种重要方法,也为乳腺癌的机制研究提供有价值的信息。

Objective To investigate the expression of p16INK4 a protein in breast cancer and analyze its clinical significance.Methods A total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4 a proteins using immunohistochemistry. Results The breast cancer samples were classified into 5 molecular subtypes, namely Luminal A（58 cases）, Luminal B（32 cases）, Her-2-positive（21 cases）, basallike（12 cases） and normal-like（9 cases） types. p16INK4 a expression was negative in 7/132（5.30%） cases, weakly positive in 15/132（11.36%） cases, positive in 40/132（30.30%） cases, and strongly positive in 70/132（53.03%） cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4 a were 16.67%（22/132） and 83.33%（110/132） in the carcinoma tissues.Statistical analysis showed the expression intensity of p16INK4 a differed significantly between the age groups（P〈0.05） but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors. Conclusion The compensatory high expression of p16INK4 a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.