Objective To explore the levels of p21Waf1/cip1and p27Kip1in functional pituitary adenomas,and analyse the relationship between the levels of p 21Waf1/cip1and p27Kip1and clinical features.Method Tissue microarray technology was performed among 6 cases with normal pituitaries, 36 invasive pituitary adenomas and 58 non-invasive pituitary adenomas. Immunohistochemistry experiment was used to detect the protein levels of p 21Waf1/cip1and p27Kip1.The clinicopathologic data of 94 patients was collected and followed up.Methylation-specific polymerase chain reaction and sequencing were detected among 3 normal pituitaries and 24 adenomas cases. Results High-p21Waf1/cip1level cases were featured by 8/36 and H-Score 148 ±28.4 in invasive functional adenomas,and 39/58 and 217.2 ±43.2 in non-invasive adenomas(χ2=18.017,P=0.000).High-p27Kip1level cases were featured by 10/36 and H-Score 122.1 ±31.1 in invasive functional adenomas, and 37/58 and 187.2 ±36.6 in non-invasive adenomas(χ2=9.446,P =0.002).The p27Kip1level was negative with serum prolactin levels in prolactinoma patients(r =-0.237,P<0.01).Average 33 CpG sites per sample were analyzed by using MALDI-TOF Mass array,and 7/33 CpG sites methylation levels of p27Kip1were higher than 50%.There were significant differences in 4 CpG sites between invasive specimens and non-invasive cases(P <0.01).Conclusion In functional pituitary adenomas,the levels of p21Waf1/cip1and p27Kip1are negatively correlated with the invasion,and promoter methylation influences the level of p 27Kip1.%目的 探讨细胞周期蛋白p21Waf1/cip1和p27Kip1在功能性垂体腺瘤中的表达,及其与患者临床特征、预后的关系.方法 构建包含6例正常垂体、36例侵袭性腺瘤(侵袭组)和58例非侵袭性腺瘤(非侵袭组)石蜡标本的组织芯片;免疫组化染色检测 p21Waf1/cip1和 p27Kip1蛋白的表达水平;MALDI-TOF 法分析p21Waf1/cip1和p27Kip1启动子甲基化水平.分析垂体腺瘤患者p21Waf1/cip1和p27Kip1蛋白表达水平与其临床特征的关系.结果 侵袭组高表达 p21Waf1/cip1者为8例(22.2%),H-Score 值为148 ±28.4;非侵袭组高表达p21Waf1/cip1者为39例(67.2%),H-Score值为217.2 ±43.2;侵袭组高表达p27Kip1者为10例(27.8%),H-Score值为122.1 ±31.1;非侵袭组高表达p27Kip1者为37例(63.8%),H-Score值为187.2 ±36.6.两组的p21Waf1/cip1和p27Kip1表达水平的差异均有统计学意义(χ2=18.01,P=0.000;χ2=11.52,P=0.001).p27Kip1表达水平与血清促乳素水平呈负相关(r=-0.237,P<0.01).CpG 位点甲基化检测显示,p27Kip1启动子甲基化水平>50%的为7/33,其中4个位点的差异有统计学意义(P<0.01).结论 功能性垂体腺瘤的p21Waf1/cip1和p27Kip1表达水平降低与肿瘤的侵袭行为有明显关系;启动子甲基化程度影响p27Kip1的表达水平.
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