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

被引:36
作者
Darcy, Kathleen M. [2 ]
Brady, William E. [2 ]
McBroom, John W. [3 ]
Bell, Jeffrey G. [4 ]
Young, Robert C. [5 ]
McGuire, William P. [6 ]
Linnolia, R. Ilona [7 ]
Hendricks, Denver [7 ]
Bonome, Tomas [7 ]
Farley, John H. [1 ]
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA
[2] GOG Stat & Data Ctr, Buffalo, NY 14263 USA
[3] GOG Hawaii MCCOP, Honolulu, HI 96859 USA
[4] Riverside Methodist Hosp, Columbus, OH 43214 USA
[5] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA
[6] Franklin Sq Hosp Ctr, Harry & Jeanette Weinberg Canc Inst, Baltimore, MD 21237 USA
[7] NCI, Ctr Canc Res, Bethesda, MD 20892 USA
关键词
p53; Overexpression; IHC; Ovarian cancer; Prognostic markers;
D O I
10.1016/j.ygyno.2008.08.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 >= 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 progress ion-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
引用
收藏
页码:487 / 495
页数:9
相关论文
共 51 条
[1]   The significance of p53 mutation and over-expression in ovarian cancer prognosis [J].
Allan, LA ;
Campbell, MK ;
Milner, BJ ;
Eccles, DM ;
Leonard, RCF ;
Parkin, DE ;
Miller, ID ;
Lessells, AM ;
Kitchener, HC ;
Haites, NE .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 1996, 6 (06) :483-490
[2]   The prognostic significance of p53 expression quantitated by computerized image analysis in epithelial ovarian cancer [J].
Anttila, MA ;
Ji, HX ;
Juhola, MT ;
Saarikoski, SV ;
Syrjänen, KJ .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 1999, 18 (01) :42-51
[3]   Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer [J].
Baekelandt, M ;
Kristensen, GB ;
Nesland, JM ;
Tropé, CG ;
Holm, R .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (07) :2061-2068
[4]   Expression and mutation of p53 in tumor effusion cells of patients with ovarian carcinoma: Response to cisplatin-based chemotherapy [J].
Bar, JK ;
Harlozinska, A ;
Popiela, A ;
Noga, L .
TUMOR BIOLOGY, 2001, 22 (02) :83-91
[5]   Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: A Gynecologic Oncology Group study [J].
Bell, Jeffrey ;
Brady, Mark F. ;
Young, Robert C. ;
Lage, Janice ;
Walker, Joan L. ;
Look, Katherine Y. ;
Rose, G. Scott ;
Spirtos, Nick M. .
GYNECOLOGIC ONCOLOGY, 2006, 102 (03) :432-439
[6]  
BERCHUCK A, 1994, AM J OBSTET GYNECOL, V170, P246
[7]   p53 and its isoforms in cancer [J].
Bourdon, J-C .
BRITISH JOURNAL OF CANCER, 2007, 97 (03) :277-282
[8]   Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies [J].
de Graeff, P. ;
Hall, J. ;
Crijns, A. P. G. ;
de Bock, G. H. ;
Paul, J. ;
Oien, K. A. ;
ten Hoor, K. A. ;
de Jong, S. ;
Hollema, H. ;
Bartlett, J. M. S. ;
Brown, R. ;
van der Zee, A. G. J. .
BRITISH JOURNAL OF CANCER, 2006, 95 (05) :627-633
[9]   p63 and p73 in human cancer: defining the network [J].
DeYoung, M. P. ;
Ellisen, L. W. .
ONCOGENE, 2007, 26 (36) :5169-5183
[10]   p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer:: A multivariate analysis [J].
Dogan, E ;
Saygili, U ;
Tuna, B ;
Gol, M ;
Gürel, D ;
Acar, B ;
Koyuncuoglu, M .
GYNECOLOGIC ONCOLOGY, 2005, 97 (01) :46-52