scholarly journals Low RAP80 mRNA Expression Correlates with Shorter Survival in Sporadic High-Grade Serous Ovarian Carcinoma

2017 ◽  
Vol 32 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Margarita Romeo ◽  
Niki Karachaliou ◽  
Imane Chaid ◽  
Cristina Queralt ◽  
Itziar De Aguirre ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Figo Stage ◽  
High Grade ◽  
Platinum Compounds ◽  
Serous Ovarian Carcinoma ◽  
Platinum Based Chemotherapy

Objective Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR–pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. Methods mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. Results Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS ( HR = 1.449, p = 0.007) and OS ( HR = 1.331, p = 0.047). Conclusions This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.

scholarly journals Clinical factors associated with prognosis in low-grade serous ovarian carcinoma: experiences at two large academic institutions in Korea and Taiwan

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun-Hyeok Kang ◽  
Yen-Ling Lai ◽  
Wen-Fang Cheng ◽  
Hyun-Soo Kim ◽  
Kuan-Ting Kuo ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Ovarian Carcinoma ◽  
Advanced Disease ◽  
Residual Disease ◽  
Figo Stage ◽  
Low Grade ◽  
High Grade ◽  
Serous Ovarian Carcinoma ◽  
Number Of Cycles

AbstractLow-grade ovarian serous carcinoma (LGSOC) has clinical features different from high-grade serous ovarian carcinoma (HGSOC) accounting for the majority of epithelial ovarian cancer. Because of its rarity, previous studies have only focused on the high-grade disease without considering the differences between the two subtypes. This study aimed to evaluate the effect of the clinical prognostic factors known for HGSOC on survival in patients with LGSOC. Based on the Federation of Gynecology and Obstetrics (FIGO) stage, progression-free survival (PFS) was markedly decreased in advanced disease compared with early disease. For stage I, patients with stage IC had poorer survival than those with stage IA and IB regardless of the number of cycles of adjuvant chemotherapy. For advanced disease, no gross residual disease after primary cytoreductive surgery was significantly associated with longer PFS when compared with gross residual disease. In multivariate analysis for PFS and overall survival (OS), age, preoperative CA-125, time interval from surgery to chemotherapy, and the number of cycles of adjuvant chemotherapy were not associated with prognosis. Complete cytoreduction was the only independent prognostic factor for PFS (HR 2.45, p = 0.045). Our study revealed that the known prognostic factors in HGSOC did not show any effect on the survival in LGSOC except for FIGO stage and complete cytoreduction.

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

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 role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 31593-31603 ◽  
Author(s):  
Euan A. Stronach ◽  
Paula Cunnea ◽  
Christina Turner ◽  
Tankut Guney ◽  
Radhika Aiyappa ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Interleukin 8 ◽  
High Grade ◽  
Serous Ovarian Carcinoma

Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma

2016 ◽  
Vol 470 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Ulrike Unger ◽  
Carsten Denkert ◽  
Ioana Braicu ◽  
Jalid Sehouli ◽  
Manfred Dietel ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Prognostic Impact ◽  
High Grade ◽  
Serous Ovarian Carcinoma

Μελέτη δεικτών μεθυλίωσης στον καρκίνο των ωοθηκών

2019 ◽  
Author(s):  
Λυδία Γιαννοπούλου
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Real Time ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Tumor Dna

Ο καρκίνος των ωοθηκών αποτελεί τον τέταρτο συχνότερα εμφανιζόμενο γυναικολογικό καρκίνο και την πέμπτη αιτία θανάτου σχετιζόμενη με καρκίνο στις γυναίκες. Χαρακτηρίζεται από αξιοσημείωτη ιστολογική και μοριακή ετερογένεια, με κυριότερο υπότυπο τον ορώδη καρκίνο ωοθηκών υψηλού βαθμού κακοήθειας (high grade serous ovarian carcinoma, HGSC), που μελετήθηκε στη διατριβή. Η παρούσα διατριβή έχει σκοπό τη μελέτη της μεθυλίωσης επιλεγμένων γονιδίων στον ορώδη καρκίνο ωοθηκών υψηλού βαθμού κακοήθειας. Τα κλινικά δείγματα που χρησιμοποιήθηκαν είναι δείγματα πρωτοπαθών όγκων, αντίστοιχα δείγματα παρακείμενων ιστών, καθώς και αντίστοιχα δείγματα κυκλοφορούντος καρκινικού DNA (circulating tumor DNA, ctDNA) από τις ίδιες ασθενείς. Οι μεθοδολογίες που εφαρμόστηκαν συνιστούν την real-time MSP για την ανίχνευση της μεθυλίωσης σε δείγματα πρωτοπαθών όγκων, παρακείμενων ιστών και πλάσματος, καθώς και την MS-HRMA για τον ημιποσοτικό προσδιορισμό της μεθυλίωσης σε δείγματα πρωτοπαθών όγκων και παρακείμενων ιστών. Αρχικά εξετάστηκε η μεθυλίωση του ογκοκατασταλτικού γονιδίου RASSF1A, όπου πραγματοποιήθηκε μία συγκριτική μελέτη σε δείγματα πρωτοπαθών όγκων, παρακείμενων ιστών και ctDNA ασθενών με HGSC. Η μεθυλίωση του γονιδίου στα δείγματα πρωτοπαθών όγκων και παρακείμενων ιστών συσχετίστηκε με σημαντικά μειωμένη ολική επιβίωση (overall survival, OS) των ασθενών. Τα συνολικά αποτελέσματα της μελέτης υπέδειξαν για πρώτη φορά την προγνωστική σημασία της μεθυλίωσης του γονιδίου στον HGSC. Στη συνέχεια, ακολούθησε μελέτη μεθυλίωσης του γονιδίου ESR1, όπου πραγματοποιήθηκε μελέτη σε δείγματα πρωτοπαθών όγκων και ctDNA ασθενών με HGSC. Η μεθυλίωση του γονιδίου στα δείγματα πρωτοπαθών όγκων συσχετίστηκε με σημαντικά αυξημένα OS και διάστημα επιβίωσης χωρίς εξέλιξη της νόσου (progression free survival, PFS) των ασθενών. H παρούσα μελέτη αποτέλεσε μία προσπάθεια αποσαφήνισης του ρόλου της μεθυλίωσης του γονιδίου στον HGSC. Ακολούθησαν οι μελέτες μεθυλίωσης γονιδίων που εμπλέκονται σε μοριακά μονοπάτια που διαταράσσονται στον HGSC, όπως τα γονίδια BRCA1 και MGMT που συμμετέχουν σε διαφορετικές πορείες επιδιόρθωσης του DNA, το γονίδιο NR2F1 που συμμετέχει ενεργά στην κυτταρική αδράνεια, τα γονίδιο RASSF10 που εμπλέκεται στην ανάπτυξη χημειοαντίστασης, καθώς και το γονίδιο RKIP που συμμετέχει στην ΕΜΤ διαδικασία. Ύστερα από τη συνολική επεξεργασία των αποτελεσμάτων, παρατηρήθηκε στατιστικά σημαντική συσχέτιση της μεθυλίωσης του γονιδίου NR2F1 στα δείγματα πρωτοπαθών όγκων, με μειωμένο PFS. Επιπλέον, η μεθυλίωση του γονιδίου BRCA1 στο ctDNA συσχετίστηκε με σημαντικά αυξημένο PFS. Τέλος, πραγματοποιήθηκε μελέτη της έκφρασης του γονιδίου PD-L1 σε δείγματα κυκλοφορούντων καρκινικών κυττάρων (circulating tumor cells, CTCs) ασθενών με HGSC, με την εφαρμογή RT-qPCR. Με βάση τα αποτελέσματα της μελέτης, παρατηρήθηκε στατιστικά σημαντική συσχέτιση της έκφρασης του γονιδίου με μειωμένη OS των ασθενών, υποδεικνύοντας μία πιθανή προγνωστική σημασία στον HGSC.

scholarly journals Overexpression of ICAM-1 Predicts Poor Survival in High-Grade Serous Ovarian Carcinoma: A Study Based on TCGA and GEO Databases and Tissue Microarray

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shasha Wang ◽  
Can Yin ◽  
Ying Zhang ◽  
Lu Zhang ◽  
Lin Tao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Adhesion Molecule ◽  
Poor Prognosis ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Poor Survival ◽  
Serous Ovarian Carcinoma

Intercellular cell adhesion molecule-1 (ICAM-1), an important adhesion molecule in the immunoglobulin superfamily, is expressed on many cell types. Recent studies have identified ICAM-1 as a potential oncogene that promotes the development of epithelial ovarian cancer (EOC); it was also found to be associated with poor survival. However, the clinical significance of its expression in high-grade serous ovarian carcinoma (HGSOC) is unclear. Thus, this study aimed to investigate the significance of ICAM-1 expression in HGSOC. Data on ICAM1 expression and mutations in serous ovarian carcinoma (SOC) were obtained from the Cancer Genome Atlas (TCGA), and ICAM1 mRNA expression data in HGSOC were obtained from the Gene Expression Omnibus (GEO) database. ICAM-1 expression was evaluated by immunohistochemistry in HGSOC and normal fallopian tube tissues microarray. In TCGA data, amplification/mutation of ICAM1 was identified in 12% of serous ovarian carcinoma samples, and overexpression of ICAM1 mRNA predicted reduced overall survival in SOC. From TCGA and GEO data, SOC patients with ICAM1 mRNA overexpression treated with chemotherapeutic drugs that contained taxol or taxol and platin together had significantly reduced progression-free survival. According to GEO data, ICAM1 mRNA expression was found significantly higher in HGSOC than in control samples. In our study, ICAM-1 overexpression was observed in 63.1% (65/103) of HGSOCs. As a prognostic biomarker, overexpression of ICAM-1 predicted reduced recurrence-free and overall survival and is an independent risk factor for poor prognosis. These findings suggest that overexpression of ICAM-I is an independent indicator of poor prognosis for HGSOC and that it can serve as an effective clinical prognostic biomarker for this disease.

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