scholarly journals Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 101042831882398
Author(s):  
Susana Ramalho ◽  
Liliana AL De Angelo Andrade ◽  
Cássio Cardoso Filho ◽  
Rodrigo de Andrade Natal ◽  
Marina Pavanello ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Figo Stage ◽  
Stage I ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Discoidin Domain Receptor ◽  
Post Surgery ◽  
Platinum Based Chemotherapy ◽  
Discoidin Domain Receptor 2

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

scholarly journals The effect of adjuvant chemotherapy on survival in patients with FIGO stage I high-grade serous ovarian cancer

2019 ◽  
Vol 153 (3) ◽  
pp. 562-567
Author(s):  
J.O.A.M. van Baal ◽  
K.K. Van de Vijver ◽  
M.D. Algera ◽  
M.A. van der Aa ◽  
G.S. Sonke ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Figo Stage ◽  
Stage I ◽  
High Grade ◽  
Serous Ovarian Cancer

Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5555-5555 ◽  
Author(s):  
Florian Heitz ◽  
Sotirios Lakis ◽  
Philipp Harter ◽  
Jalid Sehouli ◽  
Jatin Talwar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Complete Resection ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery ◽  
Tp53 Mutations ◽  
Post Surgery ◽  
Tumor Dna

5555 Background: Surgical outcome is an important prognostic factor in advanced high-grade serous ovarian cancer (HGOC). Intra-operative determination of residual disease may be prone to subjective bias. Methods: We prospectively collected and analyzed tumor tissue and plasma from 21 pts with FIGO IIIC-IV HGOC. All tumor specimen showed loss of TP53 in immunohistochemistry. Tumor DNA from tissue and peri-operative cell-free DNA at baseline (BL) and at d(ays) 1, d4 and d10 were subjected to comprehensive hybrid-capture based next-generation sequencing (NEO New Oncology GmbH, Cologne, Germany). Results: The initial cohort comprised 10 pts without (TR>0) and 11 pts with complete resection TR0, with a total of 43 somatic genomic alterations. TP53 was mutated in 20/21 (95.2%) of tissue samples and in 15/21 (71.4%) corresponding plasma samples at BL. Therefore, TP53 mutations were used as a molecular marker of circulating tumor DNA levels post-surgery. In the remaining 5 BL cases the TP53 mutations were either not present in plasma (N= 3) or rested below the detection limit (N= 2). In d1, d4 and d10 post-surgical samples, the sample specific TP53 mutations were detected in 12 out of 15, 10 out of 14 and in 7 out of 13 cases, respectively. TP53variant allele frequency (VAF) did not differ among TR0 and TR>0 at BL (mean= 1.91 versus 1.73, Mann-Whitney test p = 0.86) whereas it was significantly lower for TR0 at d1 (mean= 0.06 versus 2,06; p value= 0.002), d4 (mean= 0.07 versus 1.8; p= 0.04) and d10 (mean VAF= 0 versus 1.04; p= 0.008). Five out of 9 TR>0 cases showed at least one increase in VAF between d0 and any additional time-point. In 8 out of 9 mutations remained detectable at d10 (VAF: 0.076 – 3.26). By contrast, TR0 cases showed consistent reduction in VAF throughout the follow-up period which maximized at d10. Conclusions: Liquid biopsycan efficiently detect somatic mutations in the cfDNA of pts with HGOC following debulking surgery. Variation of the TP53 VAF in sequential post-surgical samples appears to be restricted to TR>0 cases, whereas in TR0 pts VAF progressively decreases. Liquid biopsy may hold promise as a tool for the objective determination of residual disease after debulking surgery.

Genomic profiling of the residual disease of advanced high‐grade serous ovarian cancer after neoadjuvant chemotherapy

2019 ◽  
Vol 146 (7) ◽  
pp. 1851-1861 ◽  
Author(s):  
Yong J. Lee ◽  
Dachan Kim ◽  
Jung E. Shim ◽  
Su‐Jin Bae ◽  
Yu‐Jin Jung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Genomic Profiling ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals Development of a Genomic Signatures-Based Predictor of Initial Platinum-Resistance in Advanced High-Grade Serous Ovarian Cancer Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yuan Li ◽  
Xiaolan Zhang ◽  
Yan Gao ◽  
Chunliang Shang ◽  
Bo Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Accuracy ◽  
Predictive Performance ◽  
Platinum Resistance ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Single Nucleotide Variants ◽  
Tissue Samples ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

scholarly journals SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery

2020 ◽  
Vol 7 (6) ◽  
pp. 1805094
Author(s):  
Maria Bååth ◽  
Sofia Westbom-Fremer ◽  
Laura Martin de la Fuente ◽  
Anna Ebbesson ◽  
Juliette Davis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Residual Disease ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery

scholarly journals Paraneoplastic Cerebellar Ataxia Can Affect Prognosis in High-Grade Serous Ovarian Cancer: A Case Report

2020 ◽  
Vol 13 (2) ◽  
pp. 1006-1012
Author(s):  
Aikaterini Liapi ◽  
Apostolos Sarivalasis
Keyword(s):  
Ovarian Cancer ◽  
Cerebellar Ataxia ◽  
Systemic Treatment ◽  
Residual Disease ◽  
Oncological Outcome ◽  
Favorable Effect ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Oncological Treatment ◽  
Transient Improvement

The reported case is a 61-year-old woman, admitted for gradual onset of gait disturbances and dysphonia. The serum immunological panel revealed anti-Yo autoantibodies, suggestive of a paraneoplastic syndrome (PNS). A PET-CT revealed a suspicious left ovarian mass with retroperitoneal nodal involvement, and the histological assessment of surgical samples confirmed a FIGO IIIC high-grade serous ovarian cancer (HGSOC). Deemed inoperable at first, the patient was treated by carboplatin and paclitaxel chemotherapy, after which she refused surgical debulking. At the end of her systemic treatment, the patient only experienced a transient improvement of the cerebellar ataxia. Despite the suboptimal oncological treatment, the patient still presents stable disease and is free of progression 7 years from her diagnosis. This case study illustrates the favorable effect of PNS occurrence on oncological outcome in a patient with advanced HGSOC. The absence of recurrence despite the presence of residual disease after the systemic treatment is unusual and could be related to the PNS.

scholarly journals Is BRCA mutational status a predictor of platinum-based chemotherapy related hematologic toxicity in high-grade serous ovarian cancer patients?

2019 ◽  
Vol 154 (1) ◽  
pp. 138-143 ◽  
Author(s):  
Federica Tomao ◽  
Lucia Musacchio ◽  
Federica Di Mauro ◽  
Serena Maria Boccia ◽  
Violante Di Donato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Hematologic Toxicity ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutational Status ◽  
Platinum Based Chemotherapy
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