目的:探讨子宫内膜癌中雌激素受体(estrogen receptor,ER)、孕激素受体(progestin receptor,PR)、第10染色体同源缺失性磷酸酶-张力蛋白基因(phosphatase and tension homology deleted on chromosome ten,PTEN)、p53及Ki-67的表达与临床、病理特征及预后的关系。方法:收集200例原发性子宫内膜癌患者的临床信息、组织病理、免疫组织化学结果及随访资料,进行统计学分析。结果:(1)子宫内膜癌病例中ER、PR、PTEN、p53的阳性表达率分别为86.5%、85.5%、82.1%和49.2%;Ki-67在癌灶中的阳性表达率为46.9%±24.7%。(2)妊娠次数与PR阳性表达呈负相关(r=-0.191,P=0.007),而发病年龄、分娩次数与p53阳性表达呈正相关(r=0.184,P=0.041;r=0.255,P=0.004)。(3)子宫内膜样腺癌中ER、PR、p53阳性率与其他类型内膜癌比较差异有统计学意义(P<0.01)。(4)ER阳性表达与手术病理分期呈负相关(r=-0.176,P=0.013),其中Ⅰ期患者的ER阳性率高于Ⅱ期及以上患者(P=0.015)。(5)ER、PR阳性表达与组织学分级呈负相关(r=-0.217,P=0.002;r=-0.317,P=0.000),但p53、Ki-67表达与其呈正相关(r=0.327,P=0.000;r=0.465,P=0.000);组织学Ⅲ级的ER、PR、p53、Ki-67表达与其他级别比较差异有统计学意义(P<0.01)。(6)ER阳性表达与肌层浸润深度呈负相关(r=-0.142,P=0.047),有或无深肌层浸润两者比较,ER、PR表达率差异均有统计学意义(P<0.05)。(7)多因素生存分析显示,PR表达的差异对总生存时间的影响有统计学意义(P=0.011)。结论:术前对诊断性刮宫标本进行免疫组织化学研究有助于全面了解子宫内膜癌的临床病理特征;除PR外,ER、PTEN、p53及Ki-67的表达情况对患者临床预后的预测意义较小。
Background Early stage （FIGO stage Ⅰ-Ⅱ） endometrioid endometrial adenocarcinoma （EEA） is very common in clinical practice.However,patients with the early stage EEA show various clinical behaviors due to biological heterogeneity.Hence,we aimed to discover distinct classes of tumors based on gene expression profiling,and analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters.Methods Hierarchical clustering was performed for class discovery in 28 eady stage EEA samples using a special cDNA microarray chip containing 492 genes designed for endometrial cancer.Correlations between clinicopathologic parameters and our classification were analyzed.And the significance analysis of microarrays （SAM） array was used to identify the signature genes according to the tumor grade and myometrial invasion.Results Three tumor subtypes （subtypes Ⅰ,Ⅱ and Ⅲ） were identified by hierarchical clustering,each subtype had different clinicopathological factors,such as tumor grade,myometrial invasion status,and FIGO stage.Moreover,SAM analysis showed 34 up-regulated genes in high grade tumors,and 38 up-regulated genes and 1 down-regulated in deep myometrial invasive tumors.The overlap genes between these two high-risk factors were markedly up-regulated in subtype Ⅰ,but down-regulated in subtype Ⅲ.Conclusion We have identified novel molecular subtypes in early stage EEA.Differential gene signatures characterize each tumor subtype,which could be used for recognizing the tumor risk and providing a basis for further treatment stratification.
GAO Bao-rong CHEN Yong-hua YAO Yuan-yang LI Xiao-ping WANG jian-liu WEI Li-hui
