Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Abstract

Purpose: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatinbased induction chemotherapy. Experimental Design: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1immunohistochemical expression. Results: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1expression. ERCC1and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value. Conclusion: Our results suggest that those patients characterized by low ERCC1expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1expression.

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

“…Secondly, wide heterogeneity of detection methods has been reported in studies under consideration [11][12][13][14][15][22][23][24][25][26][27][28][29][30][31][32][33]. It has been shown that ERCC1 immunodetection faces several methodological challenges including tissue processing, rates of interobserver agreement, geographic variation in protein expression and, most importantly, lack of the standardized cutoff value in semi-quantitative IHC [39][40][41].…”

“…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 covariates reported in included studies were: age and TNM stage in all studies, site [11-13, 15, 25], sex [11,22,26,30], tumor differentiation [11,13,25,30], performance status [28,30], histologic type [29,33], smoking [15,22], alcohol drinking [22], betel nuts chewing [22], HPV status [15], treatment methods [28,33], resection margin [11], extracapsular spreading [11], previous RT [30], relapse interval [30] and phosphor-mTOR expression [28]. The 6 pooled analysis showed that high ERCC1 expression was associated with shorter OS (HR = 1.95, 95% CI = 1.18 -3.21, I 2 = 70.8%, p = 0.000 for heterogeneity) ( Fig.…”

“…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.…”

Meta-analysis of Excision Repair Cross-complementation Group 1 (ERCC1) Association with Response to Platinum-based Chemotherapy in Ovarian Cancer

“…The similar mete-analysis was performed by Chen and the same conclusion was gained (Chen et al, 2010). In addition, many papers evaluated the relation between ERCC1 status and response to chemotherapy have been reported in various human cancers including Colorectal Cancer, bladder cancer, cervical cancer, Head and Neck Cancer, and most of studies showed ERCC1 expression was a predictor of response to chemotherapy (Handra-Luca et al, 2007;Braun et al, 2008;Kim et al, 2009;Ishibashi et al, 2010;Kim et al, 2010;Hayes et al, 2011;Kawashima et al, 2011;Park et al, 2011;Sun et al, 2012). In 2008, Lin et al performed a cohort study to evaluate the difference of ERCC1 protein expression levels between 36 sensitive cases and 27 resistant cases of serous ovarian cancer receiving neoadjuvant chemotherapy and demonstrated that ERCC1 protein expression levels in resistance group of serous ovarian cancer were significantly higher than those of sensitivity group, and Lin et al's study was in accordance with our meta-analysis (Lin et al, 2008).…”