Progressive derailment of cell cycle regulators in endometrial carcinogenesis

N. Horrée, P. J. Van Diest, P. Van Der Groep, D. M D S Sie-Go, A. P M Heintz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Derailments of the control mechanisms of the cell cycle can initiate carcinogenesis, and play a role in progression to cancer. Aim: To explore the expression of cell cycle proteins in normal, premalignant and malignant endometrial lesions representing the morphologically well defined stepwise model of human endometrial carcinogenesis Methods: Observational study. Paraffin-embedded specimens from inactive endometrium (n = 16), endometrial hyperplasia (n = 23) and endometrioid endometrial carcinoma (n = 39) were stained immunohistochemically for cyclin A, cyclin B1, cyclin D1, cyclin E, cdk2, p16, p21, p27, p53 and Ki67(MIB-1)). Differences in expression between the tissues, and correlation with classical prognostic factors for the carcinomas were analysed. Results: Expression of cyclin A and Ki67 gradually increased from normal through hyperplasia to carcinoma, indicating that proliferation increases over the carcinogenetic spectrum. cdk2, p16 and p21 gradually increased from normal through hyperplasia to carcinoma, indicating their potential importance in both early and late carcinogenesis. Cyclin D1, cyclin E and p53 especially increased and p27 decreased from hyperplasia to carcinoma, underlining their role in late carcinogenesis. In cancers, expression of cyclin A, p53 and Ki67 was positively correlated to grade, and cyclin A was positively correlated with cdk2, p21, Ki67, cyclin E and p53. Conclusion: During (endometrioid) endometrial carcinogenesis, there is increasing proliferation paralleled by progressive derailment of cyclin B1, cyclin D1, cyclin E, p16, p21, p27, p53, and cdk2, indicating the importance of these cell cycle regulators in endometrial carcinogenesis.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalJournal of Clinical Pathology
Volume61
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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