title: Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.
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.
authors.affiliation: 1] Department of Pathology, College of Medicine, Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan [2] Department of Pathology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
authors.forename: Hsien-Neng
authors.initials: HN
authors.lastname: Huang
authors.affiliation: 1] Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: 1] Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan [3] Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.affiliation: Department of Pathology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Lin
authors.affiliation: 1] Department of Pathology, College of Medicine, Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan [2] Department of Pathology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Ting
authors.identifier: 0000000236571652
authors.initials: KT
authors.lastname: Kuo
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D001483:Base Sequence; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D019098:Telomerase; D014157:Transcription Factors; C112476:ARID1A protein, human; C484760:PIK3CA protein, human; C509186:TERT protein, human
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