ERCC1 expression as a predictive marker of squamous cell carcinoma of the head and neck treated with cisplatin-based concurrent chemoradiation

Abstract

The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1 expression as a predictive marker of survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). ERCC1 expression was assessed by immunohistochemical staining. The median age of the 45 patients analysed was 56 years (range 27–75 years), and 82% were men; 73% of all specimens showed high expression of ERCC1. The overall tumour response rate after CCRT was 89%. The median follow-up was 53.6 months (95% CI, 34.5–72.7 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 58.7 and 61.3%, respectively. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 3-year PFS (83.3 vs 49.4%, P=0.036) and OS (91.7 vs 45.5%, P=0.013) rates. Multivariate analysis showed that low expression of ERCC1 was an independent predictor for prolonged survival (HR, 0.120; 95% CI, 0.016–0.934, P=0.043). These results suggest that ERCC1 expression might be a useful predictive marker of locally advanced SCCHN in patients treated with cisplatin-based CCRT.

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

“…41 We highlighted a predictive role of ERCC1-8092C4A polymorphism on TRG, a parameter directly related to therapy efficacy, whereas most of the researches published analyzed the prognostic role of the protein expression on overall survival and time to progression. 39,45,46 ABCB1-3435C4T polymorphism in the gene encoding for the cellular transporter MDR1 (P-gp), and ABCC2-1249G4A are implicated in multi-drug resistance and emerged in our Genetic polymorphisms predict response in rectal cancer study as predictive variants. Several chemotherapeutic agents used (raltitrexed, platinum derivatives, irinotecan, gefitinib) represent a substrate for P-gp and ABCC2 supporting a possible enhanced exposure of patients carrying the defective polymorphisms to the therapeutic effect of the drugs.…”

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

“…ERCC1 expression stratified by human papillomavirus (HPV) status in head and neck cancers. At the end, 17 studies containing 1288 patients were included in metaanalysis [11][12][13][14][15][22][23][24][25][26][27][28][29][30][31][32][33].…”

“…The association between ERCC1 expression and PFS was explored in seven datasets containing 430 patients, of whom 226 (53%) had high ERCC1 expression [12,14,22,24,30]. The pooled analysis showed that high ERCC1 expression was associated with shorter PFS for head and neck patients receiving platinum-based chemotherapy (HR = 2.39, 95% CI = 1.74 -3.28; I 2 = 0.0%, p = 0.47 for heterogeneity) ( Fig.…”

“…Besides ERCC1 plays a role in several other DNA repair pathways like homologous recombination [8], interstrand cross-link repair [9] and repair of DNA double-strand breaks (DSB) [10]. A correlation between level of ERCC1 expression and clinical outcomes of HNSCC patients treated with platinum-containing therapy has been investigated in numerous studies but the results were not consistent [11][12][13][14][15].…”

“…Six studies were performed in Asians containing 357 patients [12,22,26,[29][30]32], while four studies were conducted in Caucasians containing 230 patients [13,[23][24][25]. Low ERCC1 was associated with better ORR in Asian patients (OR = 0.29, 95% CI = 0.17 -0.52; I 2 = 31.7) while there was no association between ERCC1 expression and response to chemotherapy containing treatment in Caucasian patients (OR = 0.81, 95% CI = 0.40 -1.67; I 2 = 65.3 %) ( Table 2 and Fig.…”