Expression status of p53 and organic cation transporter 1 is correlated with poor response to preoperative chemotherapy in esophageal squamous cell carcinoma

Background Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. DNA-damaging drugs, such as cisplatin (CDDP) and 5-fluorouracil (5-FU), are most frequently used in preoperative chemotherapy for ESCC. However, the response to preoperative chemotherapy varies among patients. p53, encoded by TP53 , participates in apoptotic pathways following chemotherapy with DNA-damaging drugs, and mutation of TP53 contributes to chemoresistance. Organic cation transporter 1 (OCT1) participates in the uptake of CDDP, and its reduced expression is associated with CDDP resistance. The aim of this study was to evaluate the predictive impact of the expression status of p53 and OCT1 in response to preoperative chemotherapy in ESCC. Methods We retrospectively assessed 66 ESCC patients who received preoperative chemotherapy with CDDP/5-FU (CF) or docetaxel/CDDP/5-FU (DCF). p53 and OCT1 expression in pretreatment biopsy specimens was immunohistochemically determined and correlated with histological response to preoperative chemotherapy. Results p53 with wild-type (p53 WT-ex ) and mutant-type (p53 MT-ex ) expression patterns was identified in 40.9% and 59.1% of patients, respectively. High expression of OCT1 (OCT1 High ) was detected in 45.5%, and the remaining 54.5% showed low expression (OCT1 Low ). In a univariate analysis of the entire cohort, p53 MT-ex was significantly correlated with poor response ( P = 0.026), whereas OCT1 Low showed marginal significance ( P = 0.091). In a combined analysis, tumors with either p53 MT-ex or OCT1 Low showed a significant correlation with poor response compared with tumors with both p53 WT-ex and OCT1 High ( P < 0.001). The sensitivity, specificity, and accuracy of combined p53/OCT1 were 93.9%, 47.1%, and 81.8%, respectively. Multivariate analysis identified p53 ( P = 0.017), OCT1 ( P = 0.032), and combined p53/OCT1 ( P < 0.001) as independent predictors of histological response. When samples were stratified according to chemotherapy regimen in the univariate analysis, combined p53/OCT1 was the only significant factor for poor response in the CF ( P = 0.011) and DCF ( P = 0.021) groups, whereas p53 showed no statistical significance. Conclusions Our results suggest that either p53 MT-ex or OCT1 Low expression in pretreatment biopsy specimens may be a potential predictor of poor response to preoperative chemotherapy with the CF-based regimens in ESCC, although the specificity needs to be improved.