Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy

Abstract

Expression of excision repair cross-complementation group 1 (ERCC1), p53, or thioredoxin (TRX) is reported to be correlated with resistance to platinum-based drugs. The authors evaluated whether ERCC1, p53, or TRX expression could predict progression-free and/or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Immunohistochemistry was used to examine the expression of these three proteins in resected lung tumor samples obtained from 67 patients treated with platinum-based chemotherapy against recurrent tumors after curative resection. Immunostaining for ERCC1, p53, and TRX was positive in 29, 35, and 24 patients, respectively. Patients negative for ERCC1 had a significantly longer median progression-free (44 vs 26 weeks, P = 0.0075) and overall (73 vs 44 weeks, P = 0.0006) survival than those positive for ERCC1. Patients negative for p53 expression had a significantly longer median overall (70 vs 62 weeks, P = 0.0289), but not progression-free (37.5 vs 36 weeks, P = 0.2465), survival than those positive for p53 expression. From multivariate analysis, negative ERCC1 expression (hazard ratio [HR] = 1.3740, P = 0.0147) was a significantly favorable factor for progression-free survival, and negative ERCC1 expression (HR = 1.6533, P = 0.0018) and better performance status (HR = 1.9117, P = 0.0017) were significantly favorable factors for overall survival. This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving platinum-based chemotherapy against recurrent tumors after curative resection and can provide critical information for planning personalized chemotherapy.

Figure 1

Immunohistochemical staining of ERCC1, TRX, and p53 proteins in lung cancer tissues. Examples of positive or negative expression of each protein are shown. Expression of ERCC1 and p53 proteins was detected in the nuclei of cancer cells, and expression of TRX protein was present in the cytoplasm and nuclei. Quantitative estimation of immunohistochemical staining was judged as described in the Materials and Methods. Original magnification ×400.

Figure 2

Kaplan–Meier survival analysis for (a,b) ERCC1, (c,d) p53, and (e,f) TRX expression. Differences in (a,c,e) progression‐free survival and (b,d,f) overall survival between subgroups were analyzed using the log‐rank test.