Endometrial carcinomas with clear cells: A study of a heterogeneous group of tumors including interobserver variability, mutation analysis, and immunohistochemistry with HNF-1 beta Journal Article


Authors: Han, G.; Soslow, R. A.; Wethington, S.; Levine, D. A.; Bogomolniy, F.; Clement, P. B.; Köbel, M.; Gilks, B.; DeLair, D.
Article Title: Endometrial carcinomas with clear cells: A study of a heterogeneous group of tumors including interobserver variability, mutation analysis, and immunohistochemistry with HNF-1 beta
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. © 2015 International Society of Gynecological Pathologists.
Keywords: immunohistochemistry; adult; clinical article; human tissue; protein expression; aged; gene mutation; cancer staging; follow up; cancer diagnosis; endometrioid carcinoma; endometrium carcinoma; undifferentiated carcinoma; sensitivity and specificity; tumor differentiation; tumor marker; statistical significance; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; immunophenotyping; mixed tumor; clear cell carcinoma; hepatocyte nuclear factor 1beta; estrogen receptor; k ras protein; endometrial carcinoma; tumor classification; hnf-1β; mutations; carcinosarcoma; mixed mullerian tumor; oncogene n ras; diagnostic test accuracy study; clear cell; human; female; priority journal; article
Journal Title: International Journal of Gynecological Pathology
Volume: 34
Issue: 4
ISSN: 0277-1691
Publisher: Lippincott Williams & Wilkins  
Date Published: 2015-07-01
Start Page: 323
End Page: 333
Language: English
DOI: 10.1097/pgp.0000000000000162
PROVIDER: scopus
PUBMED: 25851704
DOI/URL:
Notes: Export Date: 3 August 2015 -- Source: Scopus
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MSK Authors
  1. Douglas A Levine
    379 Levine
  2. Robert Soslow
    790 Soslow
  3. Deborah F DeLair
    105 DeLair