Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients.
The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.
Hashiguchi
Yasunori
Y
Department of Obstetrics and Gynecology, Osaka City General Hospital, Japan.
Tsuda
Hiroshi
H
Inoue
Takeshi
T
Nishimura
Sadako
S
Suzuki
Tomoko
T
Kawamura
Naoki
N
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056767:Cyclin G2; D016213:Cyclins / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C101593:CCNG2 protein, human; D018797:Cell Cycle Proteins; D056767:Cyclin G2; D016213:Cyclins; D017671:Platinum Compounds; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53