Glucocorticoid receptor expression is associated with inferior overall survival independent of BRCA mutation status in ovarian cancer

2019 ◽  
Vol 29 (2) ◽  
pp. 357-364 ◽  
Author(s):  
Jennifer Taylor Veneris ◽  
Lei Huang ◽  
Jane E Churpek ◽  
Suzanne D Conzen ◽  
Gini F Fleming
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Glucocorticoid Receptor ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Receptor Expression ◽  
High Grade ◽  
Mutation Status ◽  
Relationship Of

ObjectiveHigh glucocorticoid receptor (GR) protein expression is associated with decreased progression-free survival in ovarian cancer patients and decreased sensitivity to chemotherapy in preclinical models. Prior studies suggest wild type BRCA1 promotes GR activation. The objective of this study was to characterize the relationship of tumor GR gene expression to outcome in ovarian cancer, and to evaluate the relationship of GR expression with BRCA status.MethodsWhole exome and whole genome sequencing, gene expression, and clinical data were obtained for high-grade serous ovarian cancers in The Cancer Genome Atlas. Cases with pathogenic somatic or germline BRCA1 or BRCA2 mutations were identified and classified as BRCA mutated. High or low glucocorticoid receptor expression was defined as expression above or below median of the GR/nuclear receptor subfamily 3 C1 (NR3C1) gene level. Overall survival was estimated by the Kaplan-Meier method and compared by Cox regression analysis.ResultsCombined germline DNA sequencing and tumor microarray expression data were available for 222 high-grade serous ovarian cancer cases. Among these, 47 had a deleterious germline and/or somatic mutation in BRCA1 or BRCA2. In multivariate analysis, high glucocorticoid receptor gene expression was associated with decreased overall survival among ovarian cancer patients, independently of BRCA mutation status. No correlation of GR/NR3C1 gene expression with BRCA mutation status or BRCA1 or BRCA2 mRNA level was observed.ConclusionsIncreased GR gene expression is associated with decreased overall survival in ovarian cancer patients, independently of BRCA mutation status. High-grade serous ovarian cancers with high GR expression and wild type BRCA have a particularly poor outcome.

Relationship of tumor glucocorticoid receptor expression with overall survival in ovarian cancer TCGA data

2017 ◽  
Vol 145 ◽  
pp. 33
Author(s):  
J.L.T. Veneris ◽  
L. Huang ◽  
J. Churpek ◽  
S.D. Conzen ◽  
G.F. Fleming
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Glucocorticoid Receptor ◽  
Receptor Expression ◽  
Relationship Of

scholarly journals High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

Radiology ◽  
2017 ◽  
Vol 285 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Mithat Gönen ◽  
Debra A. Goldman ◽  
Maura Miccò ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcomes ◽  
Brca Mutation ◽  
Ct Imaging ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutation Status

Determination of Both TP53 Mutation Status and the Amount of p53 Protein Has Limited Diagnostic Importance for Patients with Ovarian Cancer

2022 ◽  
Vol 29 ◽  
Author(s):  
Sebastian M. Klein ◽  
Maria Bozko ◽  
Astrid Toennießen ◽  
Nisar P. Malek ◽  
Przemyslaw Bozko
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tp53 Mutation ◽  
P53 Protein ◽  
Mutation Status ◽  
Tumor Tissues ◽  
Tp53 Status ◽  
Diagnostic Importance

Background: Ovarian cancer is one of the most aggressive types of gynecologic cancers. Many patients have a relapse within two years after diagnosis and subsequent therapy. Among different genetic changes generally believed to be important for the development of cancer, TP53 is the most common mutation in the case of ovarian tumors. Objective: Our work aims to compare the outcomes of different comparisons based on the overall survival of ovarian cancer patients, determination of TP53 status, and amount of p53 protein in tumor tissues. Methods: We analyzed and compared a collective of 436 ovarian patient’s data. Extracted data include TP53 mutation status, p53 protein level, and information on the overall survival. Values for p53 protein level in dependence of TP53 mutation status were compared using the Independent-Samples t-Test. Survival analyses were displayed by Kaplan-Meier plots, using the log-rank test to check for statistical significance. Results: We have not found any statistically significant correlations between determination of TP53 status, amount of p53 protein in tumor tissues, and overall survival of ovarian cancer patients. Conclusion: In ovarian tumors both determination of TP53 status as well as p53 protein amount has only limited diagnostic importance.

scholarly journals Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

2021 ◽  
Vol 28 (2) ◽  
pp. 1143-1152
Author(s):  
Michalis Liontos ◽  
Alkistis Papatheodoridi ◽  
Angeliki Andrikopoulou ◽  
Nikolaos Thomakos ◽  
Dimitrios Haidopoulos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Optimal Treatment ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery ◽  
Free Survival

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

scholarly journals Association between CT-texture-derived tumor heterogeneity, outcomes, and BRCA mutation status in patients with high-grade serous ovarian cancer

2018 ◽  
Vol 44 (6) ◽  
pp. 2040-2047 ◽  
Author(s):  
Andreas Meier ◽  
Harini Veeraraghavan ◽  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Ramon Sosa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Heterogeneity ◽  
Brca Mutation ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutation Status

scholarly journals A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yue Zhao ◽  
Shao-Min Yang ◽  
Yu-Lan Jin ◽  
Guang-Wu Xiong ◽  
Pin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Scoring System ◽  
Cox Regression ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Prognostic Signature ◽  
Clinical Value ◽  
Cox Regression Analysis

The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan–Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics study combining transcriptomic and clinical data established an 11-gene prognostic signature for robust and reproducible prediction of OS in HGSOC patients. This signature could be of clinical value for guiding therapeutic selection and individualized treatment.

scholarly journals Meta-analysis on the PARP-inhibitor olaparib reveals therapeutic efficacy in ovarian cancer independent of BRCA1/2 mutation status

2016 ◽  
Vol 2 (2) ◽  
pp. 91 ◽  
Author(s):  
Ines Vasconcelos ◽  
Oscar Gaspar
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Fallopian Tube ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
High Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Platinum Sensitive

<p> </p><div><p>Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising drugs for ovarian cancer treatment. This study investigated clinical trials of PARP inhibitors, in order to obtain a more complete prognosis of ovarian cancer patients, which is usually dependent on their <em>BRCA1/2</em> mutation status. The PubMed database was searched using the key terms “PARP inhibitor OR olaparib OR veliparib OR niraparib OR rucaparib OR (BMN 673) AND (ovarian cancer OR solid tumors)”, while narrowing the selection of the article type to “clinical trial” only. Women included in the study had been histologically diagnosed with recurrent high-grade serous ovarian-, fallopian tube- or primary peritoneal-carcinoma, regardless of the presence of <em>BRCA</em> germline mutation or platinum-sensitive disease recurrence. Data from three Phase I and eight Phase II clinical trials were obtained, two of which evaluated veliparib, eight olaparib and one niraparib. A total of 1042 patients with either high-grade serous ovarian-, fallopian tube- or primary peritoneal cancer were enrolled, of which 587 had a <em>BRCA1/2</em> germline mutation and at least 370 were platinum-sensitive. The overall response rate (ORR) for patients who underwent treatment with olaparib was 44.5% (95% confidence interval = 0.396–0.496). Patients with <em>BRCA1/2</em> mutation and those with wild-type <em>BRCA1/2</em> showed no significant difference in ORR (<em>p</em> = 0.35), even when considering solely Phase II trials (<em>p</em> = 0.13). PARP inhibitors, particularly olaparib, proved effective in the management of ovarian cancer patients. This study identified the existence of patients who presented wild-type <em>BRCA1/2</em> and possibly <em>BRCA</em>-independent homologous-recombination deficient tumors, or patients with wild-type <em>BRCA1/2</em> and tumors presenting other forms of <em>BRCA</em>ness, who benefit from treatment with olaparib.</p></div>

scholarly journals Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer

2021 ◽  
Vol 147 (5) ◽  
pp. 1421-1430
Author(s):  
L. C. Hanker ◽  
A. El-Balat ◽  
Z. Drosos ◽  
S. Kommoss ◽  
T. Karn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Resection ◽  
Sphingosine Kinase ◽  
Sphingolipid Metabolism ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Sphingosine Kinase 1 ◽  
Cancer Pathogenesis

Abstract Purpose Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. Methods Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. Results In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). Conclusion Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

Survival in advanced-stage ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5514-5514
Author(s):  
R. A. Lacour ◽  
S. N. Westin ◽  
M. S. Daniels ◽  
M. R. Milam ◽  
C. C. Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Initial Treatment ◽  
Brca Mutation ◽  
Complete Response ◽  
Advanced Stage ◽  
Ashkenazi Jewish ◽  
Brca Mutations ◽  
Brca Mutation Carriers

5514 Background: Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish BRCA founder mutations compared to sporadic ovarian cancer patients. The purpose of this study is to determine if this association exists in ovarian cancer patients with non- Ashkenazi Jewish (non-AJ) BRCA1 or BRCA2 mutations. Methods: Patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer and a BRCA1 or BRCA2 mutation, seen for genetic testing between January 1996 and October 2006, were identified from the institutional and genetics databases. Medical records were reviewed for clinical factors including response to initial chemotherapy. Response is defined as no clinical evidence of disease with normalization of serum CA-125 and no radiographic evidence of disease or a negative second-look surgery. Patients with sporadic ovarian cancer, without a family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, and year of diagnosis. Progression-free and overall survival were calculated by the method of Kaplan-Meier. Chi-square tests and univariate logistic regression were also used in the data analysis. Results: Thirty-nine advanced-stage ovarian cancer patients with non-AJ BRCA mutations and 47 matched, advanced-stage sporadic ovarian cancer patients have been analyzed. Compared to patients with sporadic ovarian cancer, non-AJ BRCA mutation carriers had a longer progression-free survival (PFS, 32.4 mos. vs. 22.1 mos., p = 0.0303) and overall survival (OS, 101.4 mos. vs. 51.3 mos., p < 0.001). Similarly, 72% of the non-AJ BRCA mutation carriers had a complete response to initial treatment, compared to 45% of the sporadic ovarian cancer patients (p = 0.01). The odds of complete response to initial treatment were 3.2 times greater in the non-AJ BRCA group than in the sporadic group (OR 3.2; 95% CI 1.27 - 8.15). Conclusions: This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations when compared to similar patients with sporadic ovarian cancer. Response to initial treatment appears to impact this improved survival. No significant financial relationships to disclose.

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