Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study.
OBJECTIVE
The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC).


METHODS
Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and mutant p53-isoforms. p53 overexpression was defined as >or=10% tumor cells exhibiting nuclear staining.


RESULTS
p53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progression-free survival (PFS) (logrank test: p=0.013; unadjusted Cox modeling: p=0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p=0.018) and grade (p=0.003), but not with age, stage, cell type or with tumor response and disease status after primary chemotherapy, PFS or OS. Adjusted Cox regression modeling demonstrated that p53 overexpression was not an independent prognostic factor for PFS or OS in either cohort.


CONCLUSIONS
p53 overexpression assessed by DO-7 immunostaining is common in early and advanced stage EOC, but has limited prognostic value in women treated with surgical staging and platinum-based combination chemotherapy.
Darcy
Kathleen M
KM
GOG Statistical and Data Center, Elm and Carlton Street, Buffalo NY 14263-0001, USA.
Brady
William E
WE
McBroom
John W
JW
Bell
Jeffrey G
JG
Young
Robert C
RC
McGuire
William P
WP
Linnoila
R Ilona
RI
Hendricks
Denver
D
Bonome
Tomas
T
Farley
John H
JH
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin