The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome

The CEBPA gene is known to be mutated or abnormally expressed in several cancers. This is the first study assessing the clinical impact of CEBPA gene status and expression on the ovarian cancer outcome. The CEBPA gene sequence was analyzed in 118 ovarian cancer patients (44 platinum/cyclophosphamide (PC)-treated and 74 taxane/platinum (TP)-treated), both in tumors and blood samples, and in blood from 236 healthy women, using PCR-Sanger sequencing and Real-Time quantitative PCR (qPCR)-based genotyping methods, respectively. The CEBPA mRNA level was examined with Reverse Transcription quantitative PCR (RT-qPCR). The results were correlated to different clinicopathological parameters. Thirty of 118 (25.4%) tumors harbored the CEBPA synonymous c.690G>T polymorphism (rs34529039), that we showed to be related to up-regulation of CEBPA mRNA levels (p=0.0059). The presence of the polymorphism was significantly associated with poor prognosis (p=0.005) and poor response to the PC chemotherapy regimen (p=0.024). In accordance, elevated CEBPA mRNA levels negatively affected patient survival (pT, p.(Thr230Thr) (rs34529039) polymorphism of the CEBPA gene, together with up-regulation of its mRNA expression, are negative factors worsening ovarian cancer outcome. Their adverse clinical effect depends on a therapeutic regimen used, which might make them potential prognostic and predictive biomarkers for response to DNA-damaging chemotherapy

Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.

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