Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium Yvette P. Geels a,1 , Louis J.M. van der Putten a, ⁎ ,1 , Angela A.G. van Tilborg a,b , Irene Lurkin c , Ellen C. Zwarthoff c , Johanna M.A. Pijnenborg d , Saskia H. van den Berg-van Erp e , Marc P.L.M. Snijders f , Johan Bulten b , Daniel W. Visscher g , Sean C. Dowdy h , Leon F.A.G. Massuger a a Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands b Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands c Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands d Department of Obstetrics and Gynecology, TweeSteden Hospital, Tilburg, The Netherlands e Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands f Department of Obstetrics and Gynecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands g Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA h Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA HIGHLIGHTS • Endometrium next to endometrioid endometrial carcinomas are mostly hyperplastic, but sometimes atrophic, which predicts a worse prognosis. • The immunohistochemical and genetic profiles of endometrioid carcinomas next to hyperplastic and atrophic endometrium was assessed and compared. • Carcinomas next to atrophic endometrium were associated with fewer KRAS mutations and loss of E-cadherin. abstract article info Article history: Received 22 August 2014 Accepted 5 March 2015 Available online xxxx Keywords: Endometrial carcinoma Endometrioid Background endometrium Immunohistochemistry Genetical Objective. Endometrial carcinomas are divided into type I endometrioid endometrial carcinomas (EECs), thought to arise from hyperplastic endometrium, and type II nonendometrioid endometrial carcinomas, thought to arise from atrophic endometrium. However, a minority (20%) of EECs have atrophic background endometrium, which was shown to be a marker of a worse prognosis. This study compares the immunohistochemical and genetic profiles of this possible third type to that of the known two types. Methods. 43 patients with grade 1 EEC and hyperplastic background endometrium (type I), 43 patients with grade 1 EEC and atrophic background endometrium (type III) and 21 patients with serous carcinoma (type II) were included (n = 107). Tissue microarrays of tumor samples were immunohistochemically stained for PTEN, L1CAM, ER, PR, p53, MLH1, PMS2, β-catenin, E-cadherin and MIB1. The BRAF, KRAS, and PIK3CA genes were analyzed for mutations. Results. A significantly higher expression of ER and PR, and a lower expression of L1CAM, p53 and MLH1 were found in type I and III compared to type II carcinomas. Expression of E-cadherin was significantly reduced in type III compared to type I carcinomas. Mutation analysis showed significantly less mutations of KRAS in type III compared to type I and II carcinomas (p b 0.01). Conclusion. There appear to be slight immunohistochemical and genetic differences between EECs with hyperplastic and atrophic background endometrium. Carcinogenesis of EEC in atrophic endometrium seems to be characterized by loss of E-cadherin and a lack of KRAS mutations. As expected, endometrioid and serous carcinomas were immunohistochemically different. © 2015 Elsevier Inc. All rights reserved. 1. Introduction Cancer of the uterine corpus is the most common gynecologic malignancy among women in the developed world. In 2012, it affected 47,130 women and caused the death of 8010 women in the US [1]. Gynecologic Oncology xxx (2015) xxx–xxx ⁎ Corresponding author at: Radboud University Medical Center, 791 Department of Obstetrics and Gynaecology, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands. Tel.: +31 243617768; fax: +31 243668597. E-mail address: Louis.vanderputten@radboudumc.nl (L.J.M. van der Putten). 1 Both authors contributed equally to this work. YGYNO-975829; No. of pages: 7; 4C: http://dx.doi.org/10.1016/j.ygyno.2015.03.007 0090-8258/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno Please cite this article as: Geels YP, et al, Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium, Gynecol Oncol (2015), http://dx.doi.org/10.1016/j.ygyno.2015.03.007