Prognostic relevance of c-MYC gene amplification and polysomy for chromosome 8 in suboptimally-resected, advanced stage epithelial ovarian cancers: a Gynecologic Oncology Group study.
OBJECTIVE
The Gynecologic Oncology Group (GOG) examined the prognostic relevance of c-MYC amplification and polysomy 8 in epithelial ovarian cancer (EOC).


METHODS
Women with suboptimally-resected, advanced stage EOC who participated in GOG-111, a multicenter randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin, and who provided a tumor block through GOG-9404 were eligible. Fluorescence in situ hybridization (FISH) with probes for c-MYC and the centromere of chromosome 8 (CEP8) was used to examine c-MYC amplification (> or =2 copies c-MYC/CEP8) and polysomy 8 (> or =4 CEP8 copies).


RESULTS
c-MYC amplification, defined as > or =2 copies c-MYC/CEP8, was observed in 29% (28/97) of EOCs and levels were ranged from 2.0-3.3 copies of c-MYC/CEP8. c-MYC amplification was not associated with patient age, race, GOG performance status, stage, cell type, grade, measurable disease status following surgery, tumor response or disease status following platinum-based combination chemotherapy. Women with vs. without c-MYC amplification did not have an increased risk of disease progression (hazard ratio [HR]=1.03; 95% confidence interval [CI]=0.65-1.64; p=0.884) or death (HR=1.08; 95% CI=0.68-1.72; p=0.745). c-MYC amplification was not an independent prognostic factor for progression-free survival (HR=1.03, 95% CI=0.57-1.85; p=0.922) or overall survival (HR=1.01, 95% CI=0.56-1.80; p=0.982). Similar insignificant results were obtained for c-MYC amplification categorized as > or =1.5 copies c-MYC/CEP8. Polysomy 8 was observed in 22 patients without c-MYC amplification and 3 with c-MYC amplification, and was associated with age and measurable disease status, but not other clinical covariates or outcomes.


CONCLUSIONS
c-MYC amplification and polysomy 8 have limited predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy.
Darcy
Kathleen M
KM
GOG Statistical and Data Center, Buffalo, NY 14263-0001, USA.
Brady
William E
WE
Blancato
Jan K
JK
Dickson
Robert B
RB
Hoskins
William J
WJ
McGuire
William P
WP
Birrer
Michael J
MJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002898:Chromosomes, Human, Pair 8; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin