Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.
Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.
Departments of Oncology and Pathology, Gynecology and Gynecological Oncology, Karolinska Hospital, Stockholm, Sweden;Genetics Department, Division of Clinical Sciences, and Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland.
H.
H
Blegen
N.
N
Einhorn
K.
K
Sjövall
A.
A
Roschke
B. M.
BM
Ghadimi
L. M.
LM
McShane
B.
B
Nilsson
K.
K
Shah
T.
T
Ried
G.
G
Auer