p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer

被引:0
作者
G Ferrandina
A Fagotti
M G Salerno
P G Natali
M Mottolese
F Maneschi
A De Pasqua
P Benedetti-Panici
S Mancuso
G Scambia
机构
[1] Catholic University of the Sacred Heart,Department of Obstetrics and Gynecology
[2] L.go Gemelli 8,Department of Human Pathology
[3] Istituto Regina Elena,undefined
[4] Libero Istituto Universitario Campus Biomedico,undefined
来源
British Journal of Cancer | 1999年 / 81卷
关键词
p53; ovarian cancer; cytoreduction; response to chemotherapy;
D O I
暂无
中图分类号
学科分类号
摘要
The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III–IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I–II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III–IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients.
引用
收藏
页码:733 / 740
页数:7
相关论文
共 226 条
[1]  
Bodner SM(1992)Expression of mutant p53 proteins in lung cancer correlates with the loss of p53 gene mutation Oncogene 7 743-749
[2]  
Minna JD(1998)Adenovirus-mediated wild-type p53 gene transfer down regulates vascular endothelial growth factor expresion and inhibits angiogenesis in human colon cancer Cancer Res 58 2288-2292
[3]  
Jensen SM(1996)Secondary surgical cytoreduction for advanced epithelial ovarian cancer Cancer 78 2049-2062
[4]  
D’Amico D(1993)Increased accumulation of p53 protein in cisplatin-resistant ovarian cell lines Int J Cancer 55 678-684
[5]  
Carbone D(1997)p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study Br J Cancer 75 230-235
[6]  
Mitsudomi T(1996)Bcl-2 expression, p53 accumulation and apoptosis in ovarian carcinomas Am J Clin Pathol 105 341-349
[7]  
Fedorko J(1997)Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer Int J Cancer 74 407-414
[8]  
Buchhagen DL(1992)Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma Br J Cancer 65 40-44
[9]  
Nau MM(1997)Quantification of p53 in epithelial ovarian cancer Gynecol Oncol 66 435-438
[10]  
Gazdar AF(1993)Use of wild type p53 to achieve complete treatment sensitization of tumor cells expressing endogenous mutant p53 Mol Carcinog 14 275-285