scholarly journals Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies

2009 ◽  
Vol 16 (4) ◽  
pp. 1241-1249 ◽  
Author(s):  
Claudio Zamagni ◽  
Ralph M Wirtz ◽  
Pierandrea De Iaco ◽  
Marta Rosati ◽  
Elke Veltrup ◽  
...  

Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan–Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.


2017 ◽  
Vol 398 (7) ◽  
pp. 765-773 ◽  
Author(s):  
Shuo Zhao ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Axel Walch ◽  
Sandra Diersch ◽  
...  

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.


2002 ◽  
Vol 20 (2) ◽  
pp. 463-466 ◽  
Author(s):  
Y. Ben David ◽  
A. Chetrit ◽  
G. Hirsh-Yechezkel ◽  
E. Friedman ◽  
B.D. Beck ◽  
...  

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 760-760
Author(s):  
Laurent Mineur ◽  
Eric François ◽  
Jean Marc Phelip ◽  
Rosine Guimbaud ◽  
Carine Plassot ◽  
...  

760 Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (< 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vladan Zivaljevic ◽  
Katarina Tausanovic ◽  
Ivan Paunovic ◽  
Aleksandar Diklic ◽  
Nevena Kalezic ◽  
...  

Background.Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine.Aim.The aim was to determine the importance of age in survival of patients with ATC.Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis.Results.The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P=0.000, OR = 0.43, 95% CI = 0.29–0.63), only patients age (P=0.023, OR = 0.68, 95% CI = 0.49–0.95) was independent prognostic factor of favorable survival in patients with ATC.Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5783
Author(s):  
Alexandros Lalos ◽  
Ornella Neri ◽  
Caner Ercan ◽  
Alexander Wilhelm ◽  
Sebastian Staubli ◽  
...  

Background: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment. Methods: We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months. Results: There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS (p = 0.008) and OS (p = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity (p = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24–0.99; p = 0.047) and OS (HR = 0.28; 95% CI 0.10–0.77; p = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles. Conclusions: The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration.


2020 ◽  
Author(s):  
Ting Jiang ◽  
Jingxian Shen ◽  
Shuang Liu ◽  
Qing Liu ◽  
Weiwei Xiao ◽  
...  

Abstract BackgroundPancreatic cancer is the fourth leading cause of cancer-related death throughout the world. For local advanced and recurrent pancreatic cancer (LAPC/LRPC), chemoradiotherapy (CRT) is a main choice which may prolong their survival and ease patients’ symptoms.MethodsWe constructed a database of 65 patients with LAPC/LRPC treated from June, 2004 to February, 2018. We used log-rank test to evaluate the different overall survival (OS) rates of all factors involved, and used cox regression model to find out independent prognostic factors for these patients.ResultsThe median OS time for 65 eligible patients was 23.6 months. 47 (72.3%) and 18 (27.7%) patients had unresectable LAPC and LRPC, and median OS time was 17.2 and 40.7 months (P= 0.02), respectively. The mean biological effective dose (BED) to gross tumor volume (GTV) was 64.8Gy (46.7-85.5 Gy). 11(16.9%) and 54(83.1%) patients had BED> 72 Gy and BED≤ 72 Gy, and their mOS was 31.8 and 21.9 months (P= 0.08), respectively. Simultaneous dose boost to interval GTV (GTVin) was applied to 23 patients (35.4%). Patients with large GTV volume (≥ 109.2 cm3) may benefit from radiation dose boost (mOS: 27.6 vs. 5.3 months, P= 0.004). Patients with symptom relief including relief of pain, jaundice, and/or diarrhea had higher OS rates than those without response (mOS: 25.7 vs. 13.2 months, P< 0.01) and multivariate cox regression analysis suggested symptom relief was the most significant prognostic factor for OS (HR= 0.44, 95%CI 0.35-2.36, P= 0.02).ConclusionCRT with simultaneous integrated boost of radiation dose may bring survival benefit for LAPC/LRPC patients with bulk tumor. Symptom relief is the most significant prognostic factor for LAPC/LRPC patients after comprehensive CRT.


2021 ◽  
pp. 1-9
Author(s):  
Yi-Chiao Liao ◽  
Yu-Che Ou ◽  
Chen-Hsuan Wu ◽  
Hung-Chun Fu ◽  
Ching-Chou Tsai ◽  
...  

BACKGROUND: CA125 level normalization at different chemotherapy cycles has been reported to be a prognosticator in advanced epithelial ovarian cancer. OBJECTIVE: In the present study, we investigated whether the time (in days) to CA125 normalization or nadir during treatment could be used as markers to predict survival. METHODS: Patients with FIGO stage III–IV epithelial ovarian cancer treated with cytoreductive surgery followed by adjuvant chemotherapy between 2008 and 2016 were enrolled in this retrospective study. Clinicopathological characteristics, changes in CA125 level during treatment, and survival outcomes were analyzed. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-off values of the time to normalization and time to nadir of CA125 levels to predict survival. Univariate and multivariate Cox regression analysis were used to examine the impact of each variable on survival. RESULTS: A total of 106 patients were included in the analysis. The optimal cut-off values for the time to normalization and nadir for predicting survival were 60 and 194 days, respectively. In Kaplan-Meier survival analysis, CA125 level normalization ⩽ 60 days and CA125 ⩽ 35 u/mL after the third cycle, and CA125 level ⩽ 10 u/mL after the sixth cycle of chemotherapy were associated with significantly better 5-year progression-free survival (PFS) and overall survival (OS). In multivariate analysis, only CA125 level normalization > 60 days was significantly associated with poor survival outcomes (PFS, HR 2.62 [95% CI: 1.54, 4.45], p= 0.004; OS, HR 2.40 [95% CI: 1.19, 4.81], p= 0.014). CONCLUSIONS: Normalization of CA125 level within 60 days after cytoreductive surgery followed by adjuvant chemotherapy in patients with advanced ovarian epithelial cancer could be used as a marker to predict survival.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5560-5560
Author(s):  
Marta Llaurado Fernandez ◽  
Amy Dawson ◽  
Hannah Kim ◽  
Nicole Lam ◽  
Maegan Bruce ◽  
...  

5560 Background: Research on ER/PR receptor function in low-grade serous ovarian cancer (LGSC) and the determinants of response to treatment are lacking. A recent study (Sehouli et al.,2018) described ER/PR immunohistochemistry (IHC) cut-points that distinguished PFS. Thus, we report on a group of patients with ER/PR expression by IHC in tumor samples of patients with LGSC and used this information to evaluate survival outcomes. Methods: Clinical information and FFPE sections were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR). Tissue microarray (TMA) sections were stained for ER/PR using standard IHC techniques (MK). 50 stage 3 and 5 stage 4 patients were analyzed. ER/PR expression was scored using a simple scoring system ( < 1% cells staining, 1-50%, and ≥ 50%) and Allred scoring. We compared Kaplan-Meier (KM) survival (PFS and OS) curves using Log rank testing and Cox regression was used to model predictive/prognostic factors. A p-value of 0.05 was considered significant. Results: The mean age of the population was 49.5 years (SD;13.7). Ninety percent of patients were treated by surgery followed by platinum-based chemotherapy (PBC). Simple scoring did not discriminate outcomes as well for ER levels. PR Allred score ( < 2, vs 2- < 6 vs ≥6) clearly discriminated KM curves for PFS (p = 0.036) and OS (p = 0.01). For Allred ER score ( < 7 vs.7- < 8 vs 8) did not distinguish PFS (p = 0.4) but notably most patients received PBC after surgery. ER Allred score significantly distinguished OS (p = 0.008). Significant factors on Cox regression for PFS were residuum (p = 0.008;95%CI:1.2-3.1) and PR (p = 0.05;95%CI:0.39-0.99), whereas for OS ER(p = 0.01:95%CI:0.2-0.8) and residuum (p = 0.04;95%CI:1-2.8). Conclusions: ER/PR expression by Allred scoring was associated with PFS and OS. Patients will benefit from much needed research on ER/PR prediction/prognosis in LGSC. This work can inform clinical trials selection/stratification and patient selection for endocrine treatment.


2014 ◽  
Vol 24 (8) ◽  
pp. 1395-1400 ◽  
Author(s):  
Vilius Rudaitis ◽  
Tadas Zvirblis ◽  
Daiva Kanopiene ◽  
Dovile Janulynaite ◽  
Laimonas Griskevicius ◽  
...  

ObjectiveThe aim of this study was to explore BRCA mutation frequency and to evaluate its impact on prognosis of advanced-stage ovarian cancer patients treated with debulking surgery and platinum-based chemotherapy.MethodsPatients with advanced-stage epithelial ovarian cancer were enrolled in a prospective, single-center study from September 2008 to December 2011. All cases were screened for BRCA1 and BRCA2 gene mutations. Progression-free survival (PFS) was assessed between BRCA1/2 mutation carriers and BRCA1/2 wild-type patients.ResultsOne hundred seven patients were enrolled and screened for BRCA1 and BRCA2 mutations; 51.4% patients were positive for BRCA1/2 gene mutation, 63.6% of which carried a single Baltic mutation, and 98.2% of them had serous histology. Older age (hazard ratio [HR], 1.032; 95% confidence interval [CI], 1.010–1.055; P = 0.0047), nonoptimal cytoreduction (HR, 3.170; 95% CI, 1.986–5.060; P < 0.0001), and BRCA1/2 wild type (HR, 1.625 [1.003–2.632]; P = 0.0486) were significantly associated with shorter PFS in multivariate Cox regression analysis. Only the nonoptimal cytoreduction was a statistically significant risk factor for shorter overall survival (HR, 2.684; 95% CI, 1.264–5.701; P= 0.0102).ConclusionsAdvanced ovarian cancer patients harboring BRCA1/2 mutation treated with debulking surgery and platinum-based adjuvant chemotherapy have a longer PFS.


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