High Excision Repair Cross-complementation Group 1 Expression Research Articles

Perspectives of ERCC1 in early-stage and advanced cervical cancer: From experiments to clinical applications.

Cervical cancer is a public health problem of extensive clinical importance. Excision repair cross-complementation group 1 (ERCC1) was found to be a promising biomarker of cervical cancer over the years. At present, there is no relevant review article that summarizes such evidence. In this review, nineteen eligible studies were included for evaluation and data extraction. Based on the data from clinical and experimental studies, ERCC1 plays a key role in the progression of carcinoma of the uterine cervix and the therapeutic response of chemoradiotherapy. The majority of the included studies (13/19, 68%) suggested that ERCC1 played a pro-oncogenic role in both early-stage and advanced cervical cancer. High expression of ERCC1 was found to be associated with the poor survival rates of the patients. ERCC1 polymorphism analyses demonstrated that ERCC1 might be a useful tool for predicting the risk of cervical cancer and the treatment-related toxicities. Experimental studies indicated that the biological effects exerted by ERCC1 in cervical cancer might be mediated by its associated genes and affected signaling pathways (i.e., XPF, TUBB3, and. To move towards clinical applications by targeting ERCC1 in cervical cancer, more clinical, in-vitro, and in-vivo investigations are still warranted in the future.

Clinicopathological correlation of the expression of excision repair cross complementation group1 (ERCC1) in oral cavity squamous cell carcinomas: an immunohistochemical study.

The nucleotide excision repair pathway is a sophisticated DNA repair mechanism that reduces DNA damage caused by exogenous factors. Excision repair cross complementation group 1 (ERCC1) is a prominent member of this pathway that maintains the genomic stability. The aim of this study is to determine the association between the immunohistochemical expression of ERCC1and the clinical and pathological features of oral cavity squamous cell carcinomas. The sections of formalin fixed paraffin embedded tissue blocks of oral squamous cell carcinomas (n=60) were immunohistochemically stained with anti-ERCC1antibody. Theassociation between the nuclear expression of ERCC1and the clinicopathological parameters of the tumors and the patient outcomes was evaluated using the chi-square test. ERCC1expression was evident in all studied cases of the oral squamous cell carcinomas. A high ERCC1expression was associated with smaller tumors, tumors without lymph node involvement and well-differentiated tumors (p<0.001). Better outcomes were associated with higher expression of ERCC1 (p=0.028). ERCC1seems to be an efficient biomarker for prognostication of oral squamous cell carcinomas. High expression of ERCC1indicates more favorable course of the disease.

Prognostic and Predictive Role of Excision Repair Cross-complementation Group 1 and Thymidylate Synthase in Colorectal Carcinoma Patients Received FOLFOX Chemotherapy: An Immunohistochemical Study.

We aim to determine the frequency of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC-1) immunohistochemical (IHC) expression and its relationship with clinicopathologic variables in colorectal carcinoma (CRC) patients. In addition, we aim to assess the correlation between TS and ERCC-1 expression and the response of these cases to oxaliplatin and 5-fluorouracil chemotherapy (FOLFOX). Fifty-one CRC patients were prepared for IHC analysis of ERCC-1 and TS protein expression. All patients received oxaliplatin and 5-fluorouracil combined chemotherapy (FOLFOX) and were followed up for 24 months. The data analysis showed that high ERCC-1 and TS expression was significantly associated with early treatment failure (P=0.020 and 0.000). In contrast, TS immunoexpression affects the disease-free survival rate (P=0.010). The presence of deep tumor invasion, distant metastasis, lymph node metastasis, and high Dukes' classification were significantly statistically associated with early treatment failure (P=0.001, 0.000, 0.041, and 0.015, respectively). Our results showed that both ERCC-1 and TS are predictive factors for early treatment failure in CRC patients. TS protein is a prognostic factor for disease-free survival rates. This supports the theory that both ERCC-1 and TS can be used to improve chemotherapeutic outcomes in CRC patients. High expression of TS and ERCC-1 helps in the identification of cases that will get fewer benefits from FOLFOX chemotherapy. As an innovative strategy, in these cases, we can use alternative chemotherapeutic regimens or add an extra agent. In addition, Dukes' classification and lymph node metastasis are predictive factors for early treatment failure. Thus, all those values can be used to predict CRC patients with bad prognosis and those who will get fewer benefits from FOLFOX.

Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial.

PurposeIdentification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection.Materials and MethodsThis post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values.ResultsAmong 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis.ConclusionThis study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy.

Background/AimsThe outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety.MethodsThis is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78.ResultsResponse rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors.ConclusionsOur findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

High excision repair cross-complementation group 1 expression is associated with favorable prognostic factors in breast cancer.

Distortion of DNA can inhibit transcription and replication, resulting in cell death. The nucleotide excision repair (NER) pathway recognizes and repairs DNA adducts. Excision repair cross-complementation group 1 (ERCC1) is a nuclease that serves a vital role in the NER pathway. Few studies have investigated ERCC1 expression in breast cancer. The aim of the present study was to analyze the association between clinicopathological features and ERCC1 expression in breast cancer. ERCC1 expression was studied in 224 invasive ductal carcinomas by immunohistochemical staining. ERCC1 expression was analyzed as an immunoreactive score, and classified into low and high expression groups. The association between immunohistochemical parameters and clinicopathological features was evaluated. High expression of ERCC1 was observed in 33 cases (14.7%) and was statistically associated with lower T stage (P=0.005), lower tumor size (P=0.001), no lymph node metastasis (P=0.044) and no lymphovascular invasion (LVI; P=0.004). Additionally, high ERCC1 expression was associated with a positive estrogen receptor (ER) (P=0.006) and progesterone receptor (PR) (P=0.001) expression status. Non-triple-negative breast carcinoma occurred more frequently in the high expression group (97%) than the low expression group; however, the difference was not statistically significant (P=0.056). Overall and disease-free survival were also not significantly different between the two groups (P=0.989 and P=0.215, respectively). In conclusion, high ERCC1 expression is statistically associated with lower T stage, smaller tumor size, no lymph node metastasis, no LVI, and positive ER and PR expression. This suggests that ERCC1 is associated with favorable prognostic parameters in breast cancer.

Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer

BackgroundAnimal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression.MethodsTo better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p).ResultsERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status (p < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence (p < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability.ConclusionThe results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors.

Abstract 3776: Examination of ERCC1 status in circulating tumor cells as a prognostic tool for patients with nasopharyngeal carcinoma

Abstract Investigation of the expression pattern of DNA-repair protein excision repair cross-complementation group 1 (ERCC1) has been reported to allow selection of patients with non-small cell lung cancer who are likely to benefit from cisplatin-based therapy. Recent evidence suggests that ERCC1 expression may also find prognostic use in patients with nasopharyngeal carcinoma (NPC). We evaluated ERCC1 expression and genotype from NPC tissues and peripheral blood mononuclear cells of patients with NPC. ERCC1 expression was detected in 61/77 cases (79.2%) with varying intensities, where high ERCC1 expression significantly associated with worse relapse-free survival (RFS) (HR 2.34, 1.06-5.16, p=0.036). In addition, the presence of ERCC1 C118T genotype was significantly associated with favorable RFS and overall survival (OS) in a subgroup of patients with undetectable post-treatment plasma EBV DNA. These findings support a prognostic role for ERCC1 examination in NPC. However, the invasive nature of obtaining biopsy samples for tumor marker studies is a major hindrance of this approach. To facilitate the investigation of ERCC1 expression in a noninvasive manner, we have developed a negative selection immunomagnetic method for isolating circulating tumor cells from patient blood. Cell line spike-in experiments reveal a mean recovery rate of 66% for NPC cells with greater than 99% removal of non-targeted blood cells. Specificity of CTC identification was confirmed by detection of the expression of the Epstein-Barr virus encoded small RNA (EBER) in the CTCs. This method also allowed the simultaneous analysis of the expression of multiple protein markers including CD45, cytokeratin and ERCC1. It is expected that the development of noninvasive methodologies for tumor marker studies will facilitate their clinical application for improved patient care and monitoring in the future. Note: This abstract was not presented at the meeting. Citation Format: Edwin P. Hui, Brigette BY Ma, KC Allen Chan, Charles ML Chan, SC Cesar Wong, Ka Fai To, Herbert HF Loong, Frankie KF Mo, Roger KC Ngan, Anthony TC Chan. Examination of ERCC1 status in circulating tumor cells as a prognostic tool for patients with nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3776. doi:10.1158/1538-7445.AM2017-3776

Evaluating the Prognostic Value of ERCC1 and Thymidylate Synthase Expression and the Epidermal Growth Factor Receptor Mutation Status in Adenocarcinoma Non-Small-Cell Lung Cancer.

The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). In total, 131 patients with AC-NSCLC were enrolled. The EGFR mutation status and ERCC1 and TS expression were evaluated through direct DNA sequencing and immunohistochemical analyses, respectively. The EGFR mutation status and ERCC1 and TS expression were the significant predictors of clinical outcomes. The EGFR mutation status was the main outcome predictor for overall survival (OS) benefits in the overall population. Further exploratory ERCC1 and TS expression analyses were conducted to provide additional insights. Low TS expression was predictive of improved OS of patients with negative EGFR-mutated advanced AC-NSCLC, whereas high ERCC1 expression resulted in poor OS in patients with positive EGFR-mutated advanced AC-NSCLC. TS and ERCC1 expression levels were effective prognostic factors for negative and positive EGFR-mutated AC-NSCLC, respectively. In conclusion, the present results indicate that the EGFR mutation status and TS and ERCC1 expression can be used as the predictors of OS after subsequent second-line treatments for AC-NSCLC.

High ERCC1 expression is associated with platinum-resistance, but not survival in patients with epithelial ovarian cancer.

The present study aimed to investigate the association between excision repair cross-complementation group 1 (ERCC1) expression and clinical resistance to platinum-based chemotherapy or clinical characteristics, including survival time, in patients with epithelial ovarian cancer (EOC). ERCC1 expression was determined by immunohistochemical staining in 92 tumor specimens from patients with EOC. The effect of ERCC1 expression on progression-free survival time (PFS) or overall survival time (OS), and its association with clinical resistance to platinum-based chemotherapy was investigated by Kaplan-Meier survival analysis, Cox regression analysis and the χ2 test. Of 92 patients with EOC, 89.13% (82/92) had ERCC1-positive tumors. The positive rate was significantly higher in platinum-resistant patients compared with those who were platinum-responding (P<0.05). The PFS and median OS were 12 and 30 months, respectively, in ERCC1 high expression patients, and 17 and 39 months, respectively, in ERCC1 low expression patients. However, there was no statistically significant difference in PFS (P=0.099) or OS (P=0.103) between the high and low expression groups. Furthermore, it was identified that ERCC1 was not an independent factor affecting the prognosis of patients with EOC based on Cox proportional hazards regression analysis. These results demonstrate that high ERCC1 expression is associated with resistance to platinum-based chemotherapy, but not with survival time, and ERCC1 protein expression is not an independent factor or the only factor affecting the prognosis of patients with EOC.

Expression of excision repair cross-complementation group 1 in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy.

The purpose of this study was to evaluate the expression of excision repair cross-complementation group 1 (ERCC1) in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with cisplatin-based induction chemotherapy. Eighty-five patients with locoregionally advanced NPC treated with cisplatin-based induction chemotherapy were included in this study. The expression level of ERCC1 protein in cancer tissues was detected by immunohistochemistry, and the expression level was divided into the high- and low-expression groups according to their expression level. The objective response rate (ORR) and the long-term disease control rate of two groups were compared between the two groups. The expression level of ERCC1 in NPC tissues was detected by immunohistochemistry. Forty-one cases had the high ERCC1 expression, and 44 cases had the low ERCC1 expression. The cases for complete response, partial response, stable disease, and progression disease were 1, 19, 21 in the ERCC1 high expression group and 3, 29, 12 for the ERCC1 low-expression group which indicated that the ORR in ERCC1 low group were significant higher than that of ERCC1 high expression group (P < 0.05). The 5-year overall survival, 5-year disease-free survival (DFS), and 5-year local recurrence-DFS were not statistical different between two group (P < 0.05); but the 5-year distant-DFS for ERCC1 low group were significant higher than ERCC1 high group (P < 0.05). Cisplatin-induced short-term ORR was decreased in nasopharyngeal carcinoma patients with high ERCC1 expression, which increased the risk of metastasis.

Excision Repair Cross-Complementation Group 1 (ERCC1): A Prognostic and Predictive Biomarker in Patients with Colorectal Cancer Receiving Adjuvant Oxaliplatin Based Chemotherapy

Background: Colorectal cancer (CRC) ranks as the third most common cancer and the third most killing cancer worldwide [1]. The addition of oxaliplatin to fluorouracil (FOLFOX) or capecitabine (CAPOX) has become a fundamental component of chemotherapeutic regimens and chemoradiation in adjuvant treatment of CRC cancer. Excision repair cross-complementation group 1 (ERCC1) encodes an enzyme that is essential for the efficient repair of DNA damage induced by platinum compounds including Oxaliplatin. Purpose: This study aims to investigate the role of ERCC1 as a predictive and prognostic marker in colorectal patients receiving oxaliplatin based chemotherapy and chemoradiation. Patients and Methods: 100 annotated stage III CRC patients were prepared as immunohistochemical (IHC) analysis of ERCC1 protein expression. All of the patients received oxaliplatin based chemotherapy. Results: Analysis of data showed that high ERCC1 expression was significantly associated with early treatment failure and disease free survival among patient with stage III CRC. Conclusion: High ERCC1 expression was an independent predictor factor of early treatment failure (P = 0.004).

The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis.

Excision repair cross-complementation group 1 (ERCC1) protein has been extensively investigated as a prognostic and predictive factor for platinum-based treatment in head and neck squamous cell carcinoma (HNSCC) but with inconsistent results. We performed the present meta-analysis to better elucidate this issue in advanced HNSCC. A literature search was conducted using the PubMed and Web of Science databases. The inclusion criteria were head and neck cancer patients with platinum-based treatment and evaluation of the correlation between ERCC1 expression and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both unadjusted and adjusted estimates]. In high vs. low pooled analyses, high ERCC1 expression was associated with unfavorable OS [hazard ratio (HR)=1.95, 95% confidence interval (CI) 1.18-3.21, p=0.009], PFS (HR=2.39, 95% CI 1.74-3.28, p=0.000) and ORR (odds ratio=0.48, 95% CI 0.23-0.98, p=0.044). In the subgroup analysis of adjusted OS estimates, ERCC1 was a predictor of shorter survival in Asians (HR=3.13, 95% CI 2.09-4.70, p=0.000) and Caucasians (HR=2.02, 95% CI 1.32-3.07, p=0.001) but of longer survival in South Americans (HR=0.17, 95% CI 0.07-0.40, p=0.000). Immunohistochemistry proved to be of predictive value irrespective of used antibody (p=0.009). In the stratified analysis according to the tumor site, ERCC1 expression was associated with OS in nasopharyngeal cancer (HR=2.72, 95% CI 1.79-4.13, p=0.000). ERCC1 has a potential to become predictive and prognostic factor enabling treatment tailoring in HNSCC patients.

Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation

Objective: ERCC1 (excision repair cross-complementation group 1) expression predicts survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation. In order to evaluate the predictive role in the adjuvant setting, we investigated ERCC1 expression in radically resected HNSCC patients who underwent surgery and cisplatin chemoradiation. Methods: ERCC1 expression levels were determined by immunohistochemistry in primary tumor tissues from 48 patients with stage III-IV cancers. The median follow-up was 38.5 months (range: 5-121). Results: High ERCC1 expression was observed in 36 (75%) patients. Univariate analysis showed that patients with high levels of ERCC1 had significantly worse disease-free survival and overall survival (OS) than patients with low levels (HR = 7.15; 95% CI, 1.68-30.35; p = 0.008 and HR = 9.90; 95% CI, 1.33-73.96; p = 0.025, respectively). In the multivariate analysis, high ERCC1 expression (HR = 7.36; 95% CI, 1.72-31.4; p = 0.007) together with high-risk category (HR = 2.69; 95% CI, 1.01-7.18; p = 0.048) were the best predictors for relapse. High ERCC1 expression was the only unfavorable independent determinant for OS (HR = 9.53; 95% CI, 1.27-71.35; p = 0.028). Conclusions: This investigation suggests that ERCC1 expression might be useful to predict prognosis in radically resected HNSCC patients treated with surgery and chemoradiation.

Predictive value of excision repair cross-complementation group 1 expression for platinum-based chemotherapy and survival in gastric cancer: a meta-analysis.

The predictive value of excision repair cross-complementation group 1 (ERCC1) gene for survival and response to platinum-based chemotherapy in gastric cancer (GC) remains controversial. We performed a meta-analysis to clarify the precise estimation of the prognostic and predictive effect of ERCC1. A systematic literature search was conducted using PubMed, ScienceDirect, Wiley and American Society of Clinical Oncology (ASCO) before March 2014. Studies analyzing survival data and/or chemotherapy response in GC by ERCC1 status were identified. The principal outcome measures were hazard ratios (HRs) for survival and relative risks (RRs) for chemotherapy response. Pooled HRs and RRs were calculated using fixed- or random-effects models according to the heterogeneity. Twenty-one studies involving 1,628 patients met our inclusion criteria. High ERCC1 expression was significantly associated with shorter overall survival (OS) and lower response to chemotherapy in advanced GC patients receiving palliative chemotherapy (HR 1.83; 95% CI 1.45-2.31; P<0.001; RR 0.49; 95% CI 0.38-0.62; P<0.001). There was no significant difference in survival between high and low ERCC1 expression in adjuvant setting (OS: HR 1.38; 95% CI 0.77-2.45; P=0.276; EFS 0.72; 95% CI 0.38-1.33; P=0.291). Some evidence of heterogeneity and possible publication bias were discovered in few meta-analyses. High ERCC1 expression might be an adverse prognostic and a drug-resistance predictive factor for advanced GC patients. However, further studies with consistent ERCC1 assessment methodology are needed.

Excision Repair Cross Complementation Group 1 and Thymidylate Synthase Expression in Patients With Mesothelioma

BackgroundWe hypothesized that in patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), high expression of excision repair cross complementation group 1 (ERCC1) and low expression of thymidylate synthase (TS) are associated with prolonged survival. Patients and MethodsConsecutive patients undergoing EPP at our institutions were reviewed. Tissue microarrays were constructed using five 1-mm cores per patient. TS and ERCC1 protein expression was evaluated by immunohistochemical techniques. The average percentage scores from evaluable cores were assessed and the median score was used to divide the group. Overall survival (OS) from the time of surgery was determined by the Kaplan-Meier method and results were compared by the log-rank test. ResultsEighty patients were included: median age, 58 years; 79% men; 76% epithelial and 24% biphasic subtypes; 25% and pathologic stage I/II and 73% stage III/IV. The median OS was 18.2 months (80% deceased at the censor date). Nineteen patients received neoadjuvant chemotherapy; 2 patients received chemotherapy with adjuvant intent and 28 patients received palliative chemotherapy. The median score was 10.2% for TS and 35% for ERCC1. There was no correlation between TS expression and OS (13.7 vs. 21.6 months for low and high levels, respectively; P = .32). There was a trend between high ERCC1 expression and longer OS (27.6 vs. 10.3 months; P = .06). ConclusionIn this series of patients with MPM undergoing EPP, TS expression was not associated with prolonged survival, but there was a trend for longer survival in patients with high ERCC1 expression.

Prognostic value of ERCC1 in head and neck carcinoma treated with definitive or adjuvant radiotherapy

To evaluate the prognostic significance of excision repair cross-complementation group 1 (ERCC1) expression in head and neck carcinoma patients treated with definitive radiotherapy (DR) or adjuvant radiotherapy (AR). ERCC1 expression was assessed by immunohistochemical staining. A total of 48 patients were assessed. High ERCC1 expression was found in 23 patients (48 %). More ERCC1-positive tumours were detected in patients treated with DR than in patients treated with AR (73 vs. 36 %, respectively, p = 0.03). ERCC1 expression had no impact on overall survival neither in the whole cohort of patients (p = 0.16) nor in each particular treatment group (AR p = 0.98; DR p = 0.21). ERCC1 expression had no predictive value in head and neck carcinoma patients treated with DR or AR. There might be difference in ERCC1 positivity that comes out of whether the assessment is done on biopsy or surgical specimens.

Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy

The aim of the present study was to evaluate the correlation between excision repair cross-complementation group 1 (ERCC1) protein with the clinical outcome of nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based induction chemotherapy. One hundred one Stage III-IVB nonkeratinizing NPC patients who were treated with cisplatin (DDP)+fluorouracil (5-Fu) induction chemotherapy were recruited. Pre-treatment tumor biopsy specimens were analyzed for ERCC1 by immunohistochemistry. The relationship of ERCC1 expression and chemotherapy response and survival of these NPC patients was analyzed. The objective response to induction chemotherapy of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 88.2% vs. 72% (P=0.041). The 5-year distant failure-free survival (D-FFS) of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 73.5% vs. 51.3% (P=0.037). ERCC1 expression was a significant prognostic factor for overall survival and D-FFS using Cox regression analysis. High tumor ERCC1 expression predicts low chemotherapy response and poor survival mainly caused by more metastasis in locoregionally advanced NPC treated with cisplatin-based induction chemotherapy.

AOS22 Expression of excision repair cross complementation group 1 (ERCC1) protein in Indonesian patients with nasopharyngeal carcinoma receiving cisplatin-based adjuvant chemotherapy

Background Overexpression of excision repair cross complementation group 1 (ERCC1) has been reported to be associated with resistance to platinum-based chemotherapy in head and neck cancer. Since cisplatin-based adjuvant chemoradiotherapy is the standard treatment for nasopharyngeal cancer (NPC) in Indonesia, it is important to investigate the role of ERCC1 as a possible predictive marker of disease progression in our patients. Methods Consecutive samples obtained from our pathology archives of NPC from 31 patients who were receiving standard treatment with cisplatin-based chemoradiotherapy were examined for ERCC1 expression by use of immunohistochemistry. A retrospective cohort study was done and overall survival curves (OS) were plotted versus expression of ERCC1. Findings ERCC1 expression was high in 16 (51.6%) patients and low in 15 (48.4%). There were no differences in the baseline characteristics between the two groups (age, sex, and stage of the disease; p > 0.05). Median survival was 15.5 months. Analysis of OS showed a significant difference between the two groups ( p = 0.02). A univariate analysis of the baseline characteristics and ERCC1 in relation to the 1 year OS showed that only ERCC1 was significant. 53.3% (95% confidence interval (CI) 40.4–66.2) of patients in the group with high ERCC1 expression had an OS of 1 year or more, whereas 80% (95% CI 69.7–90.3; p = 0.02) of the group with low ERCC1 expression had an OS of 1 year or more. The median 1 year OS in the high ERCC-1 group was 13.2 months (95% CI 0.0–27.2), whereas it was not achievable in the low ERCC-1 group. Hazard ratio for the group with high expression of ERCC1 was 3.304 (95% CI 1.12–9.71). Interpretation The low expression of ERCC1 might prolong the overall survival in Indonesian patients with NPC who are receiving standard cisplatin-based chemoradiotherapy. The authors declared no conflicts of interest.

ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis

It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58-0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93-2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39-2.22; P = 0.000; RR, 0.77; 95% CI, 0.64-0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC.