Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.
File(s)
Author(s)
Type
Journal Article
Abstract
Objective
TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas.
Methods
Statistical analyses were done with the Kaplan-Meier method, log-rank test, the Cox's and logistic regression models for all patients, and in subgroups with and without TP53 accumulation (TP53 + and TP53 −, respectively).
Results
Forty of 159 ovarian carcinomas (25.2%) were diagnosed in patients with BRCA1 germline mutations; 102 tumors (64.2%) were TP53 + and 57 (37.8%) were TP53 −. Among patients with TP53 + carcinomas, BRCA1 carriers had increased odds of recurrence compared with sporadic cases (HR 2.25, P = 0.003; median disease-free survival time 7.7 vs. 18.4 months, respectively). In the smaller TP53 − subgroup, BRCA1 mutation reduced the risk of death by 46% (HR 0.54, P = 0.099, median overall survival time 42.7 vs. 28.1 months), but beyond the border of significance. When the TP53 status was not taken into account, BRCA1 mutations did not show any significance, however, there was a trend toward increased odds of complete remission for women with BRCA1 mutations compared to non-carriers (OR 2.47, P = 0.064). Taxane-platinum therapy showed advantage over the platinum-cyclophosphamide one in the entire group of patients and in the TP53 + subgroup.
Conclusions
Our results suggest that the TP53 accumulation status determines the prognosis of BRCA1 mutation carriers with high-grade ovarian carcinomas.
TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas.
Methods
Statistical analyses were done with the Kaplan-Meier method, log-rank test, the Cox's and logistic regression models for all patients, and in subgroups with and without TP53 accumulation (TP53 + and TP53 −, respectively).
Results
Forty of 159 ovarian carcinomas (25.2%) were diagnosed in patients with BRCA1 germline mutations; 102 tumors (64.2%) were TP53 + and 57 (37.8%) were TP53 −. Among patients with TP53 + carcinomas, BRCA1 carriers had increased odds of recurrence compared with sporadic cases (HR 2.25, P = 0.003; median disease-free survival time 7.7 vs. 18.4 months, respectively). In the smaller TP53 − subgroup, BRCA1 mutation reduced the risk of death by 46% (HR 0.54, P = 0.099, median overall survival time 42.7 vs. 28.1 months), but beyond the border of significance. When the TP53 status was not taken into account, BRCA1 mutations did not show any significance, however, there was a trend toward increased odds of complete remission for women with BRCA1 mutations compared to non-carriers (OR 2.47, P = 0.064). Taxane-platinum therapy showed advantage over the platinum-cyclophosphamide one in the entire group of patients and in the TP53 + subgroup.
Conclusions
Our results suggest that the TP53 accumulation status determines the prognosis of BRCA1 mutation carriers with high-grade ovarian carcinomas.
Date Issued
2016-12-07
Date Acceptance
2016-11-15
Citation
Gynecologic Oncology, 2016, 144 (2), pp.369-376
ISSN
0090-8258
Publisher
Elsevier
Start Page
369
End Page
376
Journal / Book Title
Gynecologic Oncology
Volume
144
Issue
2
Copyright Statement
© 2016 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Obstetrics & Gynecology
Ovarian cancer
Prognosis
BRCA1
TP53 accumulation
CANCER PATIENTS
BREAST-CANCER
CLINICAL-SIGNIFICANCE
BRCA1/2 MUTATIONS
SURVIVAL
P53
PLATINUM
EXPRESSION
FEATURES
GROWTH
Publication Status
Published