PI3K/AKT signalling pathway controls important cellular processes such as the cell proliferation and apoptosis. PIK3CA gene encoding a catalytic subunit of the PI3K is mutated and/or amplified in various neoplasms, including ovarian cancer. We aimed to evaluate PIK3CA alterations and their clinical importance in ovarian cancer patients. Molecular analysis was performed on 117 ovarian carcinomas with the use of qPCR, SSCP and sequencing. In a group of 98 patients with complete clinical data, 62 patients were treated with standard taxane-platinum regimens and 36 patients with platinum-cyclophosphamide regimens. A multivariate analysis was performed by the Cox's and logistic regression models. PIK3CA mutations occurred in 5/117 (4.3%) carcinomas, exclusively in the endometrioid and clear cell types (p = 0.0002); they were also associated with low FIGO stage (p = 0.0003), low tumor grade (p = 0.045) and early patient's age at diagnosis (p = 0.0005). The PIK3CA amplification (predominantly a low-level) was found in 28/117 (24%) ovarian carcinomas. It was more frequent in TP53 mutant tumors (p = 0.012) and tended to associate with high pAKT expression (p = 0.061). The PIK3CA amplification strongly diminished odds of complete remission (OR = 0.25, p = 0.033) and platinum sensitive response (PS, OR = 0.12, p = 0.004) in the taxane-platinum treated patients. The odds of PS were also much lower in all patients with the PIK3CA amplification evaluated together, regardless of the treatment applied (OR = 0.18, p = 0.001). Our results suggest that PIK3CA amplification may be a marker predicting ovarian cancer response to chemotherapy.

BackgroundTaxane-platinum therapy (TP) has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy) in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC.MethodsWe compared the effectiveness of PC/PAC (n = 253) and TP (n = 199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)].ResultsThe advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+), and not in the TP53(-) group. In the TP53(+) group taxane-platinum therapy enhanced the probability of complete remission (p = .018), platinum sensitivity (p = .014), platinum highly sensitive response (p = .038) and longer survival (OS, p = .008). Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+) group. In the TP53(-) group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010). However, in the TP53(-) group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077). Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation.ConclusionOur results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+) tumors or older than 53 years. In the group of patients ≤53 yrs and with TP53(-) tumors platinum-based therapy is possibly equally efficient. We provide hints for planning randomized trials to verify these observations.

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Background Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNPs) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000 observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that impact prognosis are not known. The nuclear factor-kappa B (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance—p < 2.5×10−5). Results were statistically significant when assessed for patients of a single histology. Key associations were with CARD11 (caspase recruitment domain family, member 11) rs41324349 in patients with mucinous EOC (HR 1.82, 95% CI 1.41-2.35, p=4.13×10−6) and TNFRSF13B (tumor necrosis factor receptor superfamily, member 13B) rs7501462 in patients with endometrioid EOC (HR 0.68, 95% CI 0.56-0.82, p=2.33×10−5). Other associations of note included TRAF2 (TNF receptor-associated factor 2) rs17250239 in patients with high-grade serous EOC (HR 0.84, 95% CI 0.77-0.92, p=6.49×10−5) and PLCG1 (phospholipase C, gamma 1) rs11696662 in patients with clear cell EOC (HR 0.43, 95% CI 0.26-0.73, p=4.56×10−4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.

The surgical treatment of advanced ovarian cancer is based on the maximal debulking with widening the operation range to the infiltrated organs. The aims are as follows: (1) the assessment of the quantity and quality of intra- and postoperative complications in patients with advanced ovarian cancer in which partial bowel resection was performed and (2) the evaluation of intra- and postoperative complications related to surgery with bowel resection and anastomosis, compared to Hartmann's procedure. The analysis of debulking procedures with intestinal resection and postoperative period in 39 ovarian cancer patients, FIGO stage III-IV, was performed. During 39 operations, the most frequent type of resection was the sigmoidectomy or proctosigmoidectomy (29 patients). In the remaining patients, left- and right-side hemicolectomy or partial enterectomy was done. Twenty-four anastomosis and 15 Hartmann's procedures were performed. There were no differences between surgery with anastomosis and Hartmann's procedure in aspect of quantity of complications, blood loss, and the time of surgery. There were no statistically significant differences in overall survival and progression-free survival in both groups. We conclude that the percentage of complications related to debulking surgery with intestinal resection in advanced ovarian cancer patients might be accepted. The quantity of complications related to surgery with anastomosis and to Hartmann's procedure is similar. If possible, the surgery with anastomosis should be performed.

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<div>Abstract<p>Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, <i>P</i> < 2.5 × 10⁻⁵). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (<i>CARD11</i>) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41–2.35; <i>P</i> = 4.13 × 10⁻⁶] and tumor necrosis factor receptor superfamily, member 13B (<i>TNFRSF13B</i>) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56–0.82; <i>P</i> = 2.33 × 10⁻⁵). Other associations of note included TNF receptor–associated factor 2 (<i>TRAF2</i>) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77–0.92; <i>P</i> = 6.49 × 10⁻⁵) and phospholipase C, gamma 1 (<i>PLCG1</i>) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26–0.73; <i>P</i> = 4.56 × 10⁻⁴). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. <i>Cancer Epidemiol Biomarkers Prev; 23(7); 1421–7. ©2014 AACR</i>.</p></div>