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

Abstract

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.

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

“…To elucidate the mechanistic background of CM-induced radioresistance, we hypothesized that CM might influence the expression of genes involved in DNA repair or genes related to cell survival. Excision repair cross complementation group 1 (ERCC1) is a DNA-damage repair associated gene, which is involved in resolution of irradiation induced DNA breaks [ 14 ]. In SCC-25 cells, stimulation with CM increased the relative ERCC1 gene expression 5-fold (p < 0.01; Figure 2E ).…”

Lack of Correlation between Aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation

“…ERCC1 is a DNA repair gene whose protein product plays an important role in nucleotide excision repair; both its protein and mRNA expression is reduced in colon cancer and glioma [ 39 – 41 ]. On the other hand, the ERCC1 protein is known to be overexpressed in human head and neck squamous cell carcinoma and esophageal carcinoma [ 42 , 43 ]. In this study, since its protein expression disappeared upon hyperplasia irrespective of promoter methylation, the underlying causative factor might involve gene mutation, degradation of the proteins by ROS, or epigenetic change other than promoter methylation [ 40 ].…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…Some biomarkers have shown predictive value for outcomes with standard anticancer therapies, including platinum agents, cetuximab‐based chemotherapy, panitumumab‐based chemotherapy, afatinib, radiotherapy, concurrent chemoradiotherapy (CCRT), and immunotherapy . Such biomarkers are particularly important for clinical trial design, as they can aid in patient selection or stratification at randomization, serve as treatment‐monitoring tools, and help predict which specific patient groups are likely to derive the greatest benefit from a particular treatment.…”