scholarly journals ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

2014 ◽  
Vol 60 (10) ◽  
pp. 1282-1289 ◽  
Author(s):  
Jan Dominik Kuhlmann ◽  
Pauline Wimberger ◽  
Agnes Bankfalvi ◽  
Thomas Keller ◽  
Sarah Schöler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Surface ◽  
Cancer Patients ◽  
Independent Predictor ◽  
Excision Repair ◽  
Complementation Group ◽  
Primary Diagnosis ◽  
Platinum Resistance ◽  
Ercc1 Expression ◽  
Group 1

Abstract BACKGROUND Platinum resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Notably, the detection of the primary tumor-based excision repair cross-complementation group 1 (ERCC1) protein by immunohistochemistry was recently shown to be inaccurate for the prediction of platinum resistance. On the basis of the previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant, and given our hypothesis that the negative prognostic impact of CTC may arise from a cellular phenotype associated with platinum resistance, we asked whether expression of the excision repair cross-complementation group 1 (ERCC1) gene in the form of the ERCC1 transcript in CTC may be a suitable blood-based biomarker for platinum resistance. METHODS The presence of CTC was analyzed by immunomagnetic CTC enrichment (n = 143 patients) targeting the epithelial epitopes epithelial cell adhesion molecule (EPCAM) (also known as GA733-2) and mucin 1, cell surface associated (MUC1), followed by multiplex reverse-transcription PCR to detect the transcripts EPCAM, MUC1, and mucin 16, cell surface associated (MUC16) (also known as CA125), including ERCC1 transcripts in a separate approach. ERCC1 expression in primary tumors was comparatively assessed by immunohistochemistry, using the antibody 8F1. RESULTS At primary diagnosis, the presence of CTC was observed in 14% of patients and constituted an independent predictor of overall survival (OS) (P = 0.041). ERCC1-positive CTC (ERCC1+CTC) were observed in 8% of patients and constituted an independent predictor, not only for OS but also for progression-free survival (PFS) (P = 0.026 and P = 0.009, respectively). More interestingly, we discovered the presence of ERCC1+CTC at primary diagnosis to be likewise an independent predictor of platinum resistance (P = 0.010), whereas ERCC1 expression in corresponding primary tumor tissue predicted neither platinum resistance nor prognosis. CONCLUSIONS The presence of ERCC1+CTC can serve as a blood-based diagnostic biomarker for predicting platinum resistance at primary diagnosis of ovarian cancer.

ERCC1 Genotype and Phenotype in Epithelial Ovarian Cancer Identify Patients Likely to Benefit From Paclitaxel Treatment in Addition to Platinum-Based Therapy

2007 ◽  
Vol 25 (33) ◽  
pp. 5172-5179 ◽  
Author(s):  
Stephanie Smith ◽  
Dan Su ◽  
Irene A. Rigault de la Longrais ◽  
Peter Schwartz ◽  
Manuela Puopolo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Treatment Response ◽  
Cancer Patients ◽  
Excision Repair ◽  
Platinum Resistance ◽  
Platinum Based Chemotherapy ◽  
Risk Of Disease ◽  
Ercc1 Expression

Purpose To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel. Patients and Methods Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival. Results Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance. Conclusion Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.

Protein expression levels of excision repair cross-complementation group 1 and xeroderma pigmentosum D correlate with response to platinum-based chemotherapy in the patients with advanced epithelial ovarian cancer

2008 ◽  
Vol 18 (5) ◽  
pp. 1007-1012 ◽  
Author(s):  
K. Lin ◽  
D. Ye ◽  
X. Xie
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Clear Cell ◽  
Excision Repair ◽  
Cell Cancer ◽  
Complementation Group ◽  
Serous Ovarian Cancer ◽  
Expression Levels ◽  
Platinum Based Chemotherapy ◽  
Group 1

This study was undertaken to examine whether there is an association between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum D (XPD) protein expression levels and response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). The study cohort consisted of 91 consecutive patients suffering from stage III or IV disease of primary EOC from 1999 to 2004 at the Women's Hospital, School of Medicine, Zhejiang University. There were 36 sensitive cases of serous ovarian cancer, 27 resistant cases of serous ovarian cancer, 15 cases of clear cell cancer, and 13 cases with serous ovarian cancer receiving neoadjuvant chemotherapy. The ovarian tissue microsections were stained by standard immunohistochemical techniques to show ERCC1 and XPD protein expression levels. In resistance group of serous ovarian cancer, ERCC1 and XPD protein expression levels were significantly higher than those of sensitivity group, and after receiving neoadjuvant chemotherapy, they showed 23% and 32% higher than before. Meanwhile, their levels of clear cell cancer group were significantly higher than serous ovarian cancer group's. Upregulation of ERCC1 and XPD protein expression was associated with resistance process to platinum-based chemotherapy in advanced EOC. This study provided evidence that differences of nucleotide excision repair–related genes expression may have an effect on the observed differences in clinical behavior of EOC

Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17033-e17033
Author(s):  
Pauline Wimberger ◽  
Simon Passek ◽  
Theresa Link ◽  
Yana Vassileva ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Calcium Binding ◽  
Tumor Resection ◽  
High Volume ◽  
Primary Diagnosis ◽  
Platinum Resistance ◽  
Serum Samples ◽  
Platinum Based Chemotherapy

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

scholarly journals Heterogeneity of excision repair cross-complementation group 1 gene expression in non-small-cell lung cancer patients

2014 ◽  
Vol 3 (1) ◽  
pp. 227-331 ◽  
Author(s):  
SERHEY SMIRNOV ◽  
ANASTASIYA PASHKEVICH ◽  
VALERIYA LIUNDYSHEVA ◽  
ANDREY BABENKO ◽  
RAISA SMOLYAKOVA
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Excision Repair ◽  
Complementation Group ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Group 1
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