title: Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium.
abstract: 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<0.01).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Geels
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Louis.vanderputten@radboudumc.nl.
authors.forename: Louis J M
authors.initials: LJ
authors.lastname: van der Putten
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Angela A G
authors.initials: AA
authors.lastname: van Tilborg
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Lurkin
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.affiliation: Department of Obstetrics and Gynecology, TweeSteden Hospital, Tilburg, The Netherlands.
authors.forename: Johanna M A
authors.initials: JM
authors.lastname: Pijnenborg
authors.affiliation: Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Saskia H
authors.initials: SH
authors.lastname: van den Berg-van Erp
authors.affiliation: Department of Obstetrics and Gynecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Marc P L M
authors.initials: MP
authors.lastname: Snijders
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Dowdy
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
mesh_terms: D001284:Atrophy; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004714:Endometrial Hyperplasia / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry
keywords: Background endometrium; Endometrial carcinoma; Endometrioid; Genetical; Immunohistochemistry