Parallel cyclin E and cyclin A expression in neoplastic lesions of the uterine cervix

Abstract

Cyclin E levels are high during late G1 and early S-phase in normal cells. The cyclin E expression over the cell cycle in tumours is not fully known. The impact on patient outcome by high cyclin E levels during other parts of the cell cycle than late G1-and early S-phase is unknown. We set out to study the expression of cyclin E over the cell cycle in cervical carcinomas. Using immunofluorescence staining of cyclin A, digital microscopy, and digital image analysis, we determined which cells in a tissue section that were in S-or G2-phase. M-phase cells were detected by morphology. By simultaneously staining for cyclin E, we investigated the variation in cyclin E levels over the cell cycle in cervical carcinoma lesions. In a case -control study, in which each deceased patient was matched with a patient still alive and well after 45 years of follow-up, we found that the deceased patients had a considerably higher fraction of cyclin A-positive cells staining for cyclin E than the survivors (n ¼ 36). We conclude that parallel cyclin E and cyclin A expression is an indicator for poor outcome in cervical carcinomas. In addition, we investigated the expression pattern of cyclin E and cyclin A in consecutive biopsy samples from cervical carcinomas at different stages, as well as in human papillomavirus positive or negative adenocarcinomas in order to further study the cyclin E and cyclin A expression pattern in neoplastic lesions of the uterine cervix.

The Human Papillomavirus E6 Oncogene Dysregulates the Cell Cycle and Contributes to Cervical Carcinogenesis through Two Independent Activities

“…We also evaluated mouse reproductive tracts and their associated tumors for biomarkers commonly used for the diagnosis of human cervical cancers. Biomarkers included the E2F-responsive genes Mcm7, involved in DNA replication (20), and cyclin E, involved in the G 1 -S transition (21,22). We also monitored expression of the cyclin kinase inhibitor, p16.…”

The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions

“…[10] We encountered a significant relationship between LSILs and the expression of the cyclins A and E [Table 2]. …”

“…[9] It has been reported that cyclin-E and cyclin-A expression is an indicator for poor outcome in cervical carcinomas associated with HR-HPV. [10]…”

The Indicators of Predicting Disease Outcome in HPV Carcinogenesis

“…This could be explained by its complex up-regulation by both E7 and E6 oncoproteins, making cyclin A active in both S phase and late G2 phase of the cell cycle. Cyclin A1 might be a useful marker of cell proliferation most notably orchestrated by the capability of E7 to abrogate the inhibitory activity of p21CIP1/WAF1/SDI1 on CDK and proliferating cell nuclear antigendependent DNA replication necessary for the G1-S transition (Erlandsson, F. et al, 2006). Studies on cyclin A as prognostic marker are limited.…”