title: The invasive front in endometrial carcinoma: higher proliferation and associated derailment of cell cycle regulators.
abstract: The aim of the study was to explore whether expression of proliferation and hypoxia-related proteins differs in the central parts and the invasive front in endometrial carcinomas. Proliferation-associated proteins Ki67 and cyclin A; cell cycle regulators p16, p21, p53, cyclin D1, cyclin E, and cdk2; and hypoxia-inducible factor 1alpha and its downstream factors glucose transporter 1, carbonic anhydrase IX, and vascular endothelial growth factor were immunohistochemically stained in paraffin-embedded specimens from endometrioid (n = 33), mucinous (n = 1), and serous (n = 5) endometrial carcinomas. The percentages of positive cells at the invasive front and central tumor parts were scored and compared. Ki67 (P < .001), cyclin E (P = .018), p16 (P = .003), and cdk2 (.001) were expressed higher at the invasive front than centrally (Wilcoxon signed ranks test). Higher expression of these antigens at the invasive front was seen in 31 of 38 cases for Ki67, in 16 of 39 cases for cyclin E, in 15 of 39 cases for cdk2, and in 11 of 39 cases for p16. The other cell cycle proteins and the hypoxia-related factors did not show significant differences in expression between the central parts and the invasive front. Endometrial carcinomas clearly show an invasive front that is characterized by higher proliferation and progressive derailment of the cell cycle regulators cyclin E, p16, and cdk2, but not by an increased hypoxic response.
authors.affiliation: Department of Surgical Gynecology and Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Horrée
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Daisy M D S
authors.initials: DM
authors.lastname: Sie-Go
authors.forename: A Peter M
authors.initials: AP
authors.lastname: Heintz
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D019925:Cyclin A / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019394:Ki-67 Antigen