Ⅰ型子宫内膜癌组织中HIF-1α、Snail与E-cadherin的表达及临床意义

Expression and significance of Hif-1α,Snail and E-cadherin in type Ⅰ endometrial carcinoma

目的探讨I型子宫内膜癌组织中HIF-1α的表达,以及调控Snail和E-cadherin对肿瘤侵袭性生物学行为的影响。方法采用免疫组化方法,结合组织芯片技术,检测124例I型子宫内膜癌、28例内膜不典型增生、35例正常内膜组织中HIF-1α、Snail和E-cadherin的表达水平,分析三种蛋白表达之间的相关性及与临床病理因素的关系。结果 I型子宫内膜癌组织中HIF-1α、Snail和E-cadherin的表达率分别为61.3%、46.8%、36.3%,与正常内膜和不典型增生内膜组织相比,有显著统计学差异(P<0.01)。HIF-1α表达与病理分级、肿瘤肌层浸润和淋巴结转移明显相关(P<0.05)。Snail表达与FIGO分期、淋巴结转移明显相关(P<0.05)。E-cadherin的缺失与肿瘤肌层浸润和淋巴结转移显著相关(P<0.01)。I型子宫内膜癌组织中HIF-1α和Snail的表达呈明显正相关(r=0.214,P=0.017),而Snail和E-cadherin的表达存在负相关关系(r=–0.203,P=0.024)。结论 HIF-1α可能通过上调Snail的表达和抑制E-cadherin的表达在I型子宫内膜癌发生、侵袭和转移中发挥重要作用。

Objective To explore the expression and significance of HIF-1α,Snail and E-cadherin in human Type I endometrial carcinoma,and to investigate the possibility that HIF-1α over-expression may accelerate the invasion and metastasis activity of endometrioid carcinoma. Methods Immunohistochemistry and tissue microarray were employed to evaluate HIF-1α,Snail and E-cadherin expression in 124 endometrial carcinoma,28 atypical hyperplasia and 35 normal endometrium samples.Then their clinicopathological significance in the invasion and metastasis of endometrioid carcinoma was analyzed. Results The presence of HIF-1α,Snail and E-cadherin protein was 61.3%,46.8%,36.3% in Type I endometrial carcinoma,respectively.Compared with normal endometrium and atypical hyperplasia,there was a statistical significance（P0.01）.Additionally,forced expression of HIF-1α was tightly correlated with histological grade,myometrial invasion,lymph node metastasis（P0.05）,and increased expression of Snail was associated with FIGO stage and lymph node metastasis.Decreased expression of E-cadherin showed a significant correlation with myometrial invasion and lymph node metastasis（P0.01）.Furthermore,in primary endometrioid adenocarcinoma,statistical analysis confirmed a positive correlation between HIF-1α and Snail expression（r=0.214,P=0.017）,and there was a significant negative association of Snail with E-cadherin expression（r=–0.314,P0.01）. Conclusion Our findings demonstrate that HIF-1α may increase the invasion and metastasis activity by up-regulating Snail expression and reducing E-cadherin expression in Type I endometrial carcinoma.