Parallel cyclin E and cyclin A expression in neoplastic lesions of the uterine cervix.
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 >5 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 = 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.
Cancer Center Karolinska, CCK R8:04, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm 17176, Sweden. fredrik.erlandsson.fe@bayer.se
F
F
Erlandsson
H-S
HS
Martinsson-Ahlzén
K-L
KL
Wallin
A-C
AC
Hellström
S
S
Andersson
A
A
Zetterberg
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D002453:Cell Cycle; D019925:Cyclin A / Q000096:biosynthesis*; D019927:Cyclin E / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications; D011379:Prognosis; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D019925:Cyclin A; D019927:Cyclin E