Expression of p21Waf1/Cip1 predicts response and survival of esophageal cancer patients treated by chemoradiotherapy

Chemoradiotherapy is a multimodal therapy routinely used as a primary treatment for advanced esophageal cancer. However, it is beneficial only to patients who respond. To identify pretreatment markers predicting response and survival, we examined the expression of cell cycle regulatory molecules, p53, p21(Waf1/Cip1) cyclin D1, and CDC25B, in biopsy specimens from 76 patients with stage III and stage IV squamous cell carcinoma. Overexpression of p53, p21, cyclin D1 and CDC25B was observed in 58%, 30%, 28%, and 32% of patients, respectively. The expression of p21 correlated significantly with response to chemoradiotherapy (P = 0.0001). Survival of patients with p21-expressing tumors was better than that of patients with p21-negative tumors (P = 0.013). Expression of other genes was not significantly correlated with treatment response and survival. In patients with p53-negative tumors, survival of those patients with p21-positive tumors was significantly higher than that of those with p21-negative tumors (P = 0.0452), but no significant difference was found in patients with p53-positive tumors. Multivariate analysis revealed that p21 expression was an independent variable among pretreatment parameters in predicting survival. These results suggest that p21 expression is potentially useful for predicting the response to chemoradiotherapy and survival of patients with advanced esophageal squamous cell cancer.