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目的探讨正常子宫内膜组、癌前病变组和子宫内膜癌(endometrial carcinoma,EC)组中人附睾分泌蛋白4(HE4)和骨桥蛋白(OPN)的表达和相关性,及其对EC手术预后的影响。方法采用免疫组化(SP)法,检测分析2009年1月~2015年6月期间就诊于邯郸市中心医院的正常组、癌前病变组及癌组中HE4、OPN的表达情况,采用Kaplan-Meier生存分析法和Logrank检验来评价各因素与EC患者生存时间的关系,并用COX风险模型进行多因素分析。结果正常组、癌前病变组和癌组的子宫内膜组织中,HE4蛋白的阳性表达率逐渐升高分别为13.33%、32.00%、70.76%,OPN蛋白的阳性表达率也逐渐升高分别为10.00%、24.00%、63.74%,且组间比较差异有统计学意义(P<0.05)。HE4蛋白及OPN蛋白的阳性表达率在手术-病理分期、组织学分级、肌层浸润深度及有无淋巴结转移组中比较,差异均有统计学意义(P<0.05)。Spearman相关分析显示,EC中HE4蛋白的表达与OPN蛋白的表达呈正相关(r=0.397,P<0.05)。Kaplan-Meier分析显示手术-病理分期、肌层浸润深度、淋巴结转移、HE4阳性表达及OPN阳性表达5个因素与预后相关(P<0.05),年龄、组织学分级、组织学类型与预后不相关(P>0.05)。COX多因素逐步分析显示,手术-病理分期、组织学分级、肌层浸润深度、HE4阳性表达、OPN阳性表达是影响预后的显著因素,但组织学分级影响最不明显(P=0.049)。结论 HE4和OPN蛋白在EC中高表达且正相关,手术-病理分期晚、组织学分级高、肌层浸润深、HE4表达阳性、OPN表达阳性者预后差,HE4和OPN有望成为评价EC预后的重要标记。
Objective To investigate the expression and correlation of human epididymal secreting protein 4 (HE4) and osteopontin (OPN) in normal endometrium, precancerous lesions and endometrial carcinoma (EC) The impact of surgery prognosis. Methods Immunohistochemistry (SP) was used to detect the expression of HE4 and OPN in normal group, precancerous lesions group and cancer group from January 2009 to June 2015 in Handan Central Hospital. Kaplan- Meier survival analysis and Logrank test to evaluate the relationship between various factors and survival time of patients with EC and COX risk model for multivariate analysis. Results The positive expression rate of HE4 protein in endometrium of normal group, precancerous lesion group and cancer group was 13.33%, 32.00% and 70.76% respectively, and the positive expression rate of OPN protein was gradually increased 10.00%, 24.00%, 63.74%, respectively, and the difference between the two groups was statistically significant (P <0.05). The positive expression rate of HE4 protein and OPN protein in the pathological staging, histological grade, depth of myometrial invasion and lymph node metastasis were significantly different (P <0.05). Spearman correlation analysis showed that the expression of HE4 protein in EC was positively correlated with the expression of OPN protein (r = 0.397, P <0.05). Kaplan-Meier analysis showed that there were 5 factors related to prognosis (P <0.05), such as age, histological grade, histological type and prognosis, there were no correlation between prognosis and pathological stage, myometrial invasion depth, lymph node metastasis, HE4 positive expression and OPN positive expression (P> 0.05). COX multifactorial stepwise analysis showed that the pathological staging, histological grade, depth of myometrial invasion, HE4 positive expression and OPN positive expression were the significant factors affecting the prognosis, but the histological grading had the least effect (P = 0.049). Conclusions HE4 and OPN protein are highly expressed and positively correlated in EC. There are many histological grades, deep myometrial invasion, positive HE4 expression and poor prognosis of OPN. HE4 and OPN are expected to be important in evaluating the prognosis of EC mark.