Search

Simple Summary: The availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for all patients with ovarian cancer. Better prognosis was found for germline mutated ovarian cancer patients. Endometrioid and clear cell histology subtypes show more deleterious mutations in other genes. Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk® germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25–0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27–0.61 and HR 0.49; 95% CI 0.37–0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients. [ABSTRACT FROM AUTHOR]

Purpose: Hypoxia is a common phenomenon encountered in solid cancers, leading to chemotherapy resistance and therefore to aggressiveness of the disease. The homeostatic response to hypoxia is mediated by hypoxia-inducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1α in patients with primary epithelial ovarian cancer. Methods: In this multicentric study, 275 patients with advanced primary epithelial ovarian cancer were included. All patients underwent cytoreductive surgery with maximal surgical effort and adjuvant platinum-based chemotherapy. HIF1α expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay. Results: HIF1α was detected in 79.3% of the tissue samples. Patients with increased HIF1α expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1α (P=0.009, hazard ratio [HR] 2.505, 95% confidence interval [95% CI] 1.252-5.013) together with International Federation of Gynecology and Obstetrics (III versus IV) (P=0.013, HR 0.540, 95% CI 0.332-0.878), histology (P=0.007, HR 2.748, 95% CI 1.315-5.743), presence of peritoneal carcinomatosis (P=0.014, HR 2.176, 95% CI 1.170-4.046), residual tumor mass (P=0.017, HR 1.641, 95% CI 1.091-2.468), and response to platinum-based chemotherapy (P,0.001, HR 8.131, 95% CI 5.13-12.88) were independent prognosis factors for overall survival. The independent prognostic factors for progression- free survival were International Federation of Gynecology and Obstetrics stage (P=0.01), histological subtypes (P=0.016), and presence of peritoneal carcinomatosis (P,0.05). Conclusion: HIF1α overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease. [ABSTRACT FROM AUTHOR]

Background: Lifestyle seems to play an important role in endometrial cancer mortality, but it remains unclear which biomarkers are involved. The aim of this study was to assess the extent of the association between lifestyle-related biomarkers and the survival of endometrial cancer patients. Methods: A subcohort of 242 endometrial cancer patients, from a population-based study of the more than 90,000 female participants of the Vorarlberg Health Monitoring and Promotion Programme, was followed for a median duration of twelve years. Besides age, tumour staging, and histology, also pre-diagnostic levels of body mass index, blood pressure, triglycerides, total cholesterol, glucose, gamma-glutamyltransferase (GGT), and serum uric acid were analysed in Cox proportional hazards regression models to estimate multivariate mortality risks. Results: During follow-up 89 deaths occurred of which 49 were cancerrelated. Survival was associated with age, tumour stage, and histology. Of the biomarkers, log10- transformed GGT showed a large effect on cancer-related mortality (HR = 3.35, 95% CI 1.12-10.03), whereas the other parameters did not appear with significant effects after adjustment for the other factors. Conclusion: Elevated level of GGT, a lifestyle-related marker, was associated with poor survival among endometrial cancer patients [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in circulating tumor cells (CTCs) research could improve the way we diagnose, treat and monitor epithelial ovarian cancer (EOC) patients. In this study, we investigated the interplay between inflammation-induced systemic catabolic markers and the presence of CTCs and patient outcome, and showed that the presence of CTCs goes hand-in-hand with an increased protein turnover and immune activation. We integrated the information provided by measuring the plasma levels of albumin, tryptophan and its metabolite kynurenine in a combined score for cancer exhaustion (CCES). Our study indicates that not only could the CCES be a useful prognostic biomarker in women with EOC, but also that the interaction between the systemic microenvironment and CTCs is worth investigating in further studies. We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in "liquid biopsy" biomarker assessment. [ABSTRACT FROM AUTHOR]