ERCC1 as a Biological Marker Guiding Management in Malignant Pleural Mesothelioma

Abstract

Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM. Thus, identification of biomarkers that can determine or predict response to treatment is of importance. ERCC1 is one of these biomarkers. Keywords: Malignant pleural mesothelioma -ERCC1 -prognosis RESEARCH ARTICLE ERCC1 as a Biological Marker Guiding Management inERCC1 is an essential enzyme for life and one of the major proteins involved in DNA repair. The primary function of ERCC1 is nucleotide excision repair of damaged DNA. There are strong evidence coming from preclinical and clinical trials, indicating that ERCC1 has an independent predictive value regarding prognosis, response to treatment, recurrence and overall survival (Olaussen et al., 2006;Ozkan et al., 2010;Betti et al., 2011; Zhang et al., 2012; Zhang et al., 2013; Li et al., 2013; Li XD et al., 2013; Mechanicsville 2013). Although there are studies on ERCC1 expression level and effects of chemotherapy on survival in MPM from several countries, this is a relatively new topic with conclusions covering small groups (Martin et al., 2008;Righi et al., 2010; Zimling et al., 2012). 4118In the present study, we aimed to detect ERCC1 expression, a novel protein, that can be used as ...

RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin

“…Two other studies involving MPM patients treated with either pemetrexed as monotherapy, or combined with platinum did not found any association between ERCC1 expression and treatment response [26,27] ). In the same study, a survival analysis at 1 and 2 years reported higher survival rates in patients with no expression of ERCC1 when compared with patients with positive ERCC1 expression (64 and 49% vs. 40 and 0%, respectively) [28]. Remarkably, we found opposite results, with high ERCC1 expression being marker of increased survival.…”

The Predictive Value of ERCC1, RRM1, and Thymidylate Synthase in Advanced Malignant Pleural Mesothelioma Patients Treated with Platinum-Based Chemotherapy

“…Similarlary, Cihan et al, (2014) reported that 36% of patients with negative ERCC1 expression and 54% of patients with positive ERCC1 expression had disease progression . With respect to the course of treatment, the mean OS was determined to be 11.7 in patients who had positive ERCC1 expression, while it was 19.2 in patients with negative ERCC1 expression, suggesting an association between ERCC1 expression and disease prognosis.…”

“…Malignant pleural mesothelioma (MPM) is an aggressive tumor characterised with difficulty of diagnosis in early stage, poor prognosis, and no effective treatment. MPM has a growing tendency worldwide (Cihan et al, 2014), and its peak incidence is expected to occur between 2015 and 2030 (Neumann et al, 2013). Apart from cisplatin and the antifolates, most single-agent chemotherapy regimens?…”

Malignant pleural mesothelioma: diagnostic value of medical thoracoscopy and long-term prognostic analysis

“…The incidence of MPM has a growing tendency worldwide [ 17 ] and is likely to peak between the year 2015 and 2030 [ 18 ]. From July 2005 through June 2014, 833 patients with undiagnosed pleural effusions successfully underwent MT in our institute, 342 (41.1%) patients were confirmed to have malignant pleural effusion [ 6 ].…”