CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis
CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis
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DOI：
10.1038/modpathol.2016.160
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发表时间：
2017-02-01
期刊：
影响因子：
7.5
通讯作者：
Wang, Tian-Li
中科院分区：
文献类型：
--
作者：
Ayhan, Ayse;Kuhn, Elisabetta;Wang, Tian-Li
卵巢透明细胞癌是一种独特的卵巢癌类型，通常源于子宫内膜异位症，晚期疾病预后不佳，主要是由于对常规化疗的抵抗。先前的研究表明，ARID1A、PIK3CA、hTERT启动子频繁发生体细胞突变，ZNF217扩增；然而，与其侵袭性相关的分子改变在很大程度上仍然未知。本研究检测并比较了cyclin El在子宫内膜异位症相关卵巢肿瘤中的表达，旨在确定hTERT突变与ARID1A表达之间的关系，并评估这些分子改变对患者生存的影响。我们对207例肿瘤[透明细胞癌（n=120）、子宫内膜样癌（n=49）和浆液性肿瘤（n=38）]进行免疫组化，然后进行双色荧光原位杂交（n=88），并比较相同样本中ARID1A表达和hTERT启动子突变。Cyclin El过表达和CCNE1拷贝数增加分别发生在23.3%和14.8%的卵巢透明细胞癌中，但在其他子宫内膜异位症相关肿瘤中均未发现。所有CCNE1拷贝数增加的病例均表现出强烈的细胞周期蛋白El免疫反应性(P
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin El expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival. We performed immunohistochemistry on 207 tumors [clear cell carcinoma (n=120), endometrioid carcinoma (n=49), and seromucinous tumors (n=38)], followed by two-color fluorescence in situ hybridization (n=88) and compared with ARID1A expression and hTERT promoter mutations in the same samples. Cyclin El overexpression and CCNE1 copy-number gain occurred in 23.3% and 14.8% of ovarian clear cell carcinomas, respectively, but they were not detected in any of the other endometriosis-related tumors. All cases with CCNE1 copy-number gain demonstrated an intense cyclin El immunoreactivity (P