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Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.

子宫内膜和卵巢透明细胞癌中的分子改变: 端粒酶逆转录启动子突变的临床意义。

Huang HN,Chiang YC,Cheng WF,Chen CA,Lin MC,Kuo KT

Abstract

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

摘要

近来,在一些类型的肿瘤中发现端粒酶逆转录(TERT)启动子突变。少量研究发现在卵巢透明细胞癌中存在TERT启动子突变,但是该突变在子宫内膜透明细胞癌中未见报道。本研究旨在比较子宫内膜和卵巢透明细胞癌分子改变及临床特征的不同,并确定其对预后的影响。我们在56例卵巢透明细胞癌和14例子宫内膜透明细胞癌中评价TERT启动子突变、PIK3CA的突变、ARID1A的表达以及和其他临床病理特征的关系。结果发现,TERT启动子在子宫内膜透明细胞癌中有21% (3/14)存在突变,在卵巢透明细胞癌中16% (9/56)存在突变。相比卵巢透明细胞癌来说,子宫内膜透明细胞癌表现出平均年龄更大(P<0.001),存在ARID1A免疫反应(P = 0.017)和偶发PIK3CA基因突变(P = 0.025)。卵巢透明细胞癌中,TERT启动子突变与病人年龄>45 (P=0.045)和ARID1A表达(P=0.003)相关。子宫内膜透明细胞癌中,TERT启动子突变与其他临床病理特征没有相关性。FIGO分期较早(I期和II期)的卵巢透明细胞癌患者中,TERT启动子突变是独立的预后因子,与较短的无进展生存期和总生存期相关(P值分别为P=0.015和P=0.009)。FIGO分期较早的复发性卵巢透明细胞癌患者,TERT启动子突变与6个月内早期复发相关(P=0.018)。

我们的结论是,子宫内膜和卵巢透明细胞癌中存在TERT启动子突变。子宫内膜和卵巢透明细胞癌不同的分子改变模式提示在这些形态相似的肿瘤中存在不同的肿瘤发生过程。FIGO分期较早的卵巢透明细胞癌患者,若存在TERT启动子突变,那么要求在化疗后的最初6个月内密切随访。

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