Prognostic Significance of p53 Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study Export

@article{citeulike:6083392, abstract = {Purpose: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. Patients and Methods: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. Results: There were 81 patients (74\%) with a single mutation, three patients (3\%) with two mutations, and 25 patients (23\%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11\% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70\% reduction in risk of death (P = .014) and a 60\% reduction in risk of disease progression (P = .014) for women with such mutations. However, these striking risk reductions increased over time (P < .02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100\%) with only missense mutation(s), seven patients (32\%) with truncation mutations, and eight patients (40\%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. Conclusion: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome. 10.1200/JCO.2003.11.052}, author = {Havrilesky, Laura and Darcy, Kathleen M. and Hamdan, Hasnah and Priore, Roger L. and Leon, Jorge and Bell, Jeffrey and Berchuck, Andrew}, citeulike-article-id = {6083392}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2003.11.052}, citeulike-linkout-1 = {http://jco.ascopubs.org/content/21/20/3814.abstract}, citeulike-linkout-2 = {http://jco.ascopubs.org/content/21/20/3814.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/14551300}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=14551300}, day = {15}, doi = {10.1200/JCO.2003.11.052}, journal = {J Clin Oncol}, keywords = {and, cancer, ovarian, p53}, month = {October}, number = {20}, pages = {3814--3825}, posted-at = {2009-11-07 22:29:27}, priority = {2}, title = {Prognostic Significance of p53 Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study}, url = {http://dx.doi.org/10.1200/JCO.2003.11.052}, volume = {21}, year = {2003} }

TY - JOUR ID - citeulike:6083392 L3 - citeulike-article-id:6083392 N2 - Purpose: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. Patients and Methods: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. Results: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P = .014) and a 60% reduction in risk of disease progression (P = .014) for women with such mutations. However, these striking risk reductions increased over time (P < .02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. Conclusion: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome. 10.1200/JCO.2003.11.052 IS - 20 JF - J Clin Oncol EP - 3825 TI - Prognostic Significance of p53 Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study VL - 21 SP - 3814 KW - and KW - cancer KW - ovarian KW - p53 AU - Havrilesky, Laura AU - Darcy, Kathleen AU - Hamdan, Hasnah AU - Priore, Roger AU - Leon, Jorge AU - Bell, Jeffrey AU - Berchuck, Andrew PY - 2003/10/15/ UR - http://dx.doi.org/10.1200/JCO.2003.11.052 ER -