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High-Grade Endometrial Carcinoma: Serous and Grade 3 Endometrioid Carcinomas Have Different Immunophenotypes and Outcomes

Alkushi, Abdulmohsen M.D.; Köbel, Martin M.D.; Kalloger, Steve E. B.Sc.; Gilks, C. Blake M.D.

International Journal of Gynecological Pathology: July 2010 - Volume 29 - Issue 4 - p 343-350
doi: 10.1097/PGP.0b013e3181cd6552

High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid (EC-3), serous (SC), and clear cell carcinomas (CCC). There are conflicting data about the prognosis of these subtypes of high-grade endometrial carcinoma; this may be a result of lack of reproducibility in classifying tumor cell type. The purpose of this study was to examine differences in immunophenotype and outcome in a series of high-grade endometrial carcinomas, focusing on the comparison of EC-3 versus SC. We selected 180 endometrial carcinomas of SC, EC, or CCC type. No mixed carcinomas were included in the study. We chose the following immunohistochemical markers, estrogen receptor (ER), insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), p16, p53, progesterone receptor (PR), and phosphatase and tensin homolog (PTEN) as being significantly differentially expressed in endometrial carcinoma subtypes. The tumors were stratified into 4 groups on the basis of their cell type and grade: EC grade 1 or 2, EC-3, SC, and CCC. Univariate survival analysis revealed significant differences in outcome between the 4 groups (P<0.0001), with significantly longer disease-specific survival for grade 1 or 2 EC versus EC-3 (P=0.0001), and EC-3 versus SC (P=0.0003). p16, PTEN, and IMP3 expression was observed more frequently in SC compared with EC-3 (P<0.0001, P=0.021, and P=0.031, respectively). These 3 markers showed the highest sensitivity and specificity in distinguishing between EC-3 and SC, with receiver operating characteristics area under the curve of 0.85, 0.69, and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in EC-3 versus SC (P=0.055 and P=0.068, respectively). A combination of p16 and PTEN predicts EC-3 versus SC with a sensitivity of 90.0% and specificity of 96.8%. p16 and PTEN can aid in distinguishing between EC-3 and SC of the endometrium, and are superior to ER, PR, and p53 for this purpose. EC-3 carcinomas have a significantly better prognosis than SC carcinomas of the endometrium.

Department of Pathology (A.A.), King Fahad National Guard Hospital, Riyadh, Saudi Arabia

Department of Pathology and Laboratory Medicine (M.K.), University of Calgary, AB

Genetic Pathology Evaluation Centre of the Prostate Research Centre and Department of Pathology (S.E.K., C.B.G.), Vancouver General Hospital and University of British Columbia, Vancouver BC, Canada

Address correspondence and reprint requests to C. Blake Gilks, MD, Department of Pathology, 855 West 12th Avenue, 1st Floor JPPN, Vancouver Hospital and Health Science Centre, Vancouver, BC V5Z 1M9, Canada. E-mail:

©2010International Society of Gynecological Pathologists