结直肠癌P27表达与Ki-67、P170、MLH1、MSH2、MSH6的关系及意义

目的:探讨P27表达与结直肠癌侵袭转移、多药耐药及预后的关系,并初步分析其机制.方法:随机选取北京大学肿瘤医院结直肠外科2008-03/2012-03收治的散发性结直肠癌患者263例,所有病例均经组织学证实,全部肿瘤病例术前均未行放化疗.应用免疫组织化学SP法检测大肠癌组织中P27、Ki-67、P170、MLH1、MSH2和MSH6的表达;并结合其临床病理特征进行回顾性分析.结果:P27、Ki-67、P170、MLH1、MSH2和MSH6在结直肠癌组织中的阳性表达率依次为71.1%、81.4%、82.5%、86.7%、87.8%和71.1%.P27蛋白表达与患者性别、年龄、肿瘤的大体形态无关;而其表达缺失与肿瘤的大小、部位、分化类型、侵袭深度、脉管癌栓和淋巴结转移密切相关.P27表达与Ki-67(r=-0.315,P=0.00)、P170(r=-0.163,P=0.01)呈明显的负相关.而P27与MLH1(r=0.129,P=0.03)、MSH2(r=0.136,P=0.03)、MSH6(r=0.159,P=0.01)的表达均呈明显的正相关.结论:P27蛋白与结直肠癌发生发展、侵袭转移密切相关,其状态与结直肠癌MSI状态密切相关.P27蛋白的检测可以作为一个反映结直肠癌疾病进展的重要指标,并对临床化疗用药和预防多药耐药具有一定的指导意义.

P27 expression in colorectal cancer: Significance and correlation with expression of Ki-67, P170, MLH1, MSH2, and MSH6

AIM: To investigate the relationship between P27 expression and tumor invasion,metastasis,multidrug resistance and prognosis of colorectal cancer(CRC),and to explore the possible mechanisms involved.METHODS: Two hundred and sixty-three sporadic CRC patients who underwent surgery in the Department of Colorectal Surgery,Beijing Cancer Hospital from March 2008 to March 2012 were included in this study.All patients were diagnosed by histological examination and did not undergo chemoradiotherapy before surgery.Immunohistochemistry was used to detect P27,Ki-67,P170,MLH1,MSH2 and MSH6 protein expression in samples from these patients.The association between expression and clinical data was analysed retrospectively.RESULTS: The positive rates of P27,Ki-67,P170,MLH1,MSH2 and MSH6 expression in CRC were 71.1%,81.4%,82.5%,86.7%,87.8% and 71.1%,respectively.Deficient expression of P27 was closely associated with tumour size,location,differentiation,invasion depth,vascular invasion and lymph node metastasis,but had no association with patients’ gender,age,or tumor macroscopic morphology.P27 expression was negatively correlated with Ki-67 and P170 expression(r =-0.315,-0.163,P = 0.00,0.01),but positively with MLH1,MSH2 and MSH6 expression(r = 0.129,0.136,0.159,P = 0.03,0.03,0.01).CONCLUSION: P27 expression is closely associated with the development,invasion and metastasis of CRC.P27 protein expression can be regarded as an important parameter for evaluation of colorectal cancer progression and for selection of chemotherapy drugs and prevention of multidrug resistance.