title: Should endometrial clear cell carcinoma be classified as Type II endometrial carcinoma?
abstract: Endometrial clear cell carcinomas (ECCCs) are considered to be Type II endometrial carcinomas, like uterine serous adenocarcinoma (SCA), and therefore aggressive clinical management is indicated. However, according to the limited clinical, immunohistochemical, and molecular data available in the literature, ECCCs show overlapping features of SCA and endometrioid adenocarcinomas. Therefore, questions regarding their designation as the Type II carcinomas have been raised. We performed immunohistochemical staining for hepatocyte nuclear factor-1β and napsin A for the histologic confirmation of clear cell carcinoma (CCC), and analyzed immunohistochemical findings for estrogen receptor, progesterone receptor, HER2/neu, p53, p16, ARID1A, PTEN, DNA mismatch-repair proteins along with other prognostic factors. We performed DNA sequencing for the K-RAS, BRAF, PIK3CA, and PTEN genes for 16 pure CCCs. No patients with pure CCC experienced recurrent disease or died of the disease (0/16, 0%). ECCCs had SCA-like features with rare expression of estrogen receptor/progesterone receptor (18.8%/6.3%) and no K-RAS mutations, intermediate features regarding expressions of p53 (37.5%) and p16 (25%), and endometrioid adenocarcinoma-like features regarding losses of PTEN (81.3%), ARID1A (25%) and mismatch-repair protein (68.8%), expression of microsatellite instability-high (25%), HER2/neu (12.5%), and PIK3CA mutations (18.8%). Pure ECCC should not be regarded as Type II carcinoma, because it shares the immunohistochemical and molecular characteristics of Type I endometrioid adenocarcinoma and Type II SCA.
authors.affiliation: Departments of Obstetrics and Gynecology (H.S.B., J.Y.S.), Korea University Anam Hospital Pathology (I.K.), Korea University College of Medicine Department of Pathology (H.K.), Cheil General Hospital, Kwandong University College of Medicine Department of Pathology (S.Y.K.), Keimyung University Hospital Department of Pathology (K-R.K.), Asan Medical Center, Seoul, Korea.
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Bae
authors.forename: Hyesun
authors.initials: H
authors.lastname: Kim
authors.forename: Sun
authors.initials: S
authors.lastname: Young Kwon
authors.forename: Kyu-Rae
authors.initials: KR
authors.lastname: Kim
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Song
authors.forename: Insun
authors.initials: I
authors.lastname: Kim
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D004717:Endometrium / Q000473:pathology; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf