乳腺癌组织中Ser10磷酸化p27^kip1的表达及意义  

Expression and clinical significance of Ser10 phosphorylated p27^kip1 protein in human breast carcinoma

作　　者：郭志琴[1] 吕青山[2] 王振[1] 陆丽慧[1] 陆宁[1] 温晓伟[1] 邬万新[1] 姚明[3] 

机构地区：[1]浙江省嘉兴市第一医院病理科,314000 [2]浙江省嘉兴市第一医院检验科,314000 [3]浙江省嘉兴市第一医院麻醉与疼痛医学中心,314000

出　　处：《中华医学杂志》2017年第18期1396-1399,共4页National Medical Journal of China

基　　金：浙江省自然科学基金项目（LY16H090016）;浙江省医学重点学科建设计划（GJJX-010-001）;嘉兴市医学重点支撑学科建设计划（04-Z-01）;嘉兴市科技计划项目（2013AY21042-3）

摘　　要：目的观察第10位丝氨酸磷酸化p27^kip1（P-p27Ser10）在乳腺癌组织中的表达情况，探讨其表达的临床病理意义。方法回顾性收集嘉兴市第一医院2004年1月至2005年12月行手术切除的111例乳腺癌组织标本，采用免疫组织化学EnVision二步法检测乳腺癌及相应癌旁正常组织中P-p27Ser10的表达情况并分析其与临床病理特征的相关性；提取6例新鲜乳腺癌手术标本的总蛋白并进行定量，蛋白质印迹检测乳腺癌组织与癌旁正常组织中P-p27Ser10和p27的表达；采用免疫共沉淀方法检测乳腺癌组织中P-p27Ser10与相关蛋白Jab1的结合情况。结果免疫组织化学及蛋白质印迹结果均显示，P-p27Ser10在乳腺癌组织中的表达显著高于在癌旁正常组织中的表达，本组乳腺癌组织中P-p27Ser10阳性表达率为88．3％（98／111），癌旁组织中为7．2％（8／111），两组之间差异有统计学意义（P〈0．05）；P—p27Serl0蛋白表达与肿瘤大小、腋淋巴结转移和TNM分期有关（均P〈0．05）；P—p27Ser1O与增殖指标硒-67表达呈显著正相关（r=0．582，P〈0．05），与p27表达呈负相关（r=-0．426，P〈0．05）；免疫共沉淀结果显示，在乳腺癌组织中，P—p27Ser10与Jabl蛋白结合明显增加。结论p27Ser10磷酸化参与了乳腺癌的发生发展，与乳腺癌患者的腋淋巴结转移和TNM分期有关。联合检测P—p27Ser10和p27可为乳腺癌的临床诊断及预后判断提供重要参考价值。Objective To explore the expression and clinicopathologieal significance of Ser10 phosphorylated p27^kip1 （P-p27Ser10） protein in human breast carcinoma tissue. Methods Tissue specimens were obtained from 111 cases with breast carcinoma from January 2004 to December 2005. And the expression of P-p27Ser10 protein for each specimen was detected by immunohistochemical （EnVision） analysis. Six representative paired samples of cancerous and paired adjacent normal tissues were collected and detected by Western blot. The relationships between the expression levels of P-p27Ser10 protein and its clinieopathological characteristics in primary breast carcinoma were retrospectively analyzed. The association of P-p27Ser10 and Jabl protein was detected by eo-immunoprecipitation method. Results A high-level expression of P-p27Ser10 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of P-p27Ser10 protein was as high as 88.3% （98/111 ） and 7.2% （ 8/111 ） in cancerous and paired adjacent normal tissues respectively （P〈 0.05 ）. P-p27Ser10 expression was correlated with tumor size, lymph node metastasis and TNM stage （ all P 〈 0.05）. P-p27Ser10 expression was significantly correlated with Ki-67 （ r = 0. 582, P 〈 0. 05 ）, and inversely correlated with p27 （ r = -0. 426, P 〈0. 05）. Co-immunoprecipitation revealed that the association of P-p27Ser10 and Jabl protein was increased in breast carcinoma. Conclusion Over-expression of P-p27Ser10 protein might play an important role in the pathogenesis of breast carcinoma. P-p27Ser10 protein therefore represents a novel diagnostic marker and therapeutic target in patients with breast carcinoma.

关 键 词：乳腺肿瘤 磷酸化 P27^KIP1 临床病理特征 预后 

分 类 号：R737.9[医药卫生—肿瘤]