title: Endometrial Carcinomas With Clear Cells: A Study of a Heterogeneous Group of Tumors Including Interobserver Variability, Mutation Analysis, and Immunohistochemistry With HNF-1β.
abstract: Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.
authors: Department of Laboratory Medicine and Pathology (G.H.), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON Department of Pathology and Laboratory Medicine (P.B.C., B.G.), University of British Columbia, Vancouver, BC Department of Pathology and Laboratory Medicine (M.K.), University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada Department of Pathology (R.A.S., D.D.) Gynecology Service (S.W., D.A.L., F.B.), Department of Surgery, Memorial Sloan Kettering Cancer Center Weill Cornell Medical College (R.A.S., D.A.L.), New York, New York.
authors: Guangming
authors: G
authors: Han
authors: Robert A
authors: RA
authors: Soslow
authors: Stephanie
authors: S
authors: Wethington
authors: Douglas A
authors: DA
authors: Levine
authors: Faina
authors: F
authors: Bogomolniy
authors: Philip B
authors: PB
authors: Clement
authors: Martin
authors: M
authors: Köbel
authors: Blake
authors: B
authors: Gilks
authors: Deborah
authors: D
authors: DeLair
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015588:Observer Variation
chemical_list: D014408:Biomarkers, Tumor; D051539:Hepatocyte Nuclear Factor 1-beta