Correlation of p53 Mutations with Resistance to Platinum-based Chemotherapy and Shortened Survival in Ovarian Cancer
Purpose: The p53 tumor suppressor gene plays a central role in cell cycle regulation and induction of apoptosis. We analyzed p53 alterations and their impact on response to chemotherapy and clinical outcome in ovarian cancer patients. Experimental Design: One hundred seventy-eight ovarian carcinomas...
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Published in | Clinical cancer research Vol. 7; no. 10; pp. 2984 - 2997 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.10.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: The p53 tumor suppressor gene plays a central role in cell cycle regulation and induction of apoptosis. We analyzed p53 alterations and their impact on response to chemotherapy and clinical outcome in ovarian cancer patients.
Experimental Design: One hundred seventy-eight ovarian carcinomas, snap frozen and stored at −80°C, were analyzed for mutations of the p53 gene (exons 2–11) by single-strand conformation polymorphism and DNA sequencing and for p53 overexpression by immunohistochemistry
(monoclonal antibody DO7).
Results: p53 mutations were found in 56% (99 of 178) of the tumors, and 62% of these were located in evolutionary highly conserved domains
of the gene. Time to progression and overall survival were significantly shortened in patients with p53 mutations compared with wild-type p53 ( P = 0.029 and P = 0.014) and patients with mutations in highly conserved domains as opposed to nonconserved domains or wild-type p53 ( P = 0.010 and P = 0.007). p53 protein overexpression (>10% positively stained nuclei) was found in 62% (110 of 178). Time to progression
and overall survival were shorter in cases with p53 overexpression (cutpoint, 10%: P = 0.071 and P = 0.056) but only marginally significant. Resistance to adjuvant cisplatin or carboplatin chemotherapy was significantly
more frequent in patients with p53 overexpression ( P = 0.001) or p53 missense mutations ( P = 0.008) than patients with normal p53.
Conclusions: p53 alterations correlate significantly with resistance to platinum-based chemotherapy, early relapse, and shortened overall
survival in ovarian cancer patients in univariate analysis. In multivariable analysis though, p53 was not an independent prognostic
factor. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |