title: Molecular profiles of benign and (pre)malignant endometrial lesions.
abstract: Endometrial carcinomas are histologically classified as endometrioid, assumed to originate from hyperplastic endometrium, or non-endometrioid carcinomas, assumed to originate from atrophic endometrium. However, both on a histological and a molecular level there are indications that there are more carcinoma types and carcinogenetic pathways. This study aims to analyze endometrial carcinogenesis on a molecular level. The presence of known KRAS, PIK3CA, AKT1, CTNNB1, BRAF, EGFR and NRAS mutations was studied in proliferative, atrophic and hyperplastic endometrium, endometrioid and serous carcinomas, and the endometrium next to these carcinomas, using single molecule Molecular Inversion Probes. Mutations were found in 9 (15%) of the 62 non atypical, and in 6 (18%) of the 34 atypical hyperplasia cases. In comparison, mutations were found in 1 (3%) of the simple, and 8 (30%) of the 27 complex hyperplasia cases. In 12/22 (55%) endometrioid carcinomas, a mutation was found. The KRAS gene was most often mutated in carcinomas next to hyperplastic endometrium, whereas PIK3CA and CTNNB1 mutations were found in endometrioid carcinomas with adjacent atrophic endometrium. Complex hyperplasia rather than atypical hyperplasia appears to be the most important lesion in the carcinogenesis of endometrioid carcinomas, and KRAS, PIK3CA and CTNNB1 mutations appear to play an important role in this process. Carcinogenesis of endometrioid carcinomas next to hyperplasia seems to be different to that of those next to atrophia. The value of these findings in managing endometrial hyperplasia and carcinoma should be studied.
authors.affiliation: Department of Obstetrics and Gynaecology and.
authors.forename: Louis J M
authors.initials: LJM
authors.lastname: van der Putten
authors.affiliation: Department of Obstetrics and Gynaecology and.
authors.forename: Renée
authors.initials: R
authors.lastname: van Hoof
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Pathology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
authors.forename: Bastiaan B J
authors.initials: BBJ
authors.lastname: Tops
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Obstetrics and Gynaecology and.
authors.forename: Marc P L M
authors.initials: MPLM
authors.lastname: Snijders
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Pathology, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands.
authors.forename: Saskia H
authors.initials: SH
authors.lastname: van den Berg-van Erp
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Pathology, St. Elisabeth Hospital, 5022GC Tilburg, The Netherlands and.
authors.forename: Anneke A M
authors.initials: AAM
authors.lastname: van der Wurff
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Pathology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.affiliation: Department of Obstetrics and Gynaecology and.|Department of Obstetrics and Gynaecology, TweeSteden Hospital, 5042AD Tilburg, The Netherlands.
authors.forename: Johanna M A
authors.initials: JMA
authors.lastname: Pijnenborg
authors.affiliation: Department of Obstetrics and Gynaecology and.
authors.forename: Leon F A G
authors.initials: LFAG
authors.lastname: Massuger
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011230:Precancerous Conditions / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D014591:Uterine Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras)