Preoperative radiotherapy modulates ezrin expression and its value as a predictive marker in patients with rectal cancer

Summary The purpose of this study was to assess the value of ezrin expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Operative samples from 176 rectal cancer patients and 76 diagnostic preoperative biopsies from the same cohort were analyzed for ezrin expression using immunohistochemistry. The patients had received short- (n = 76) or long-course radiotherapy with (n = 36) or without chemotherapy (n = 10) or no treatment preoperatively (n = 54). The direct effect of radiation on ezrin expression was studied in cultured cells by Western blot analysis. The biopsies and respective operative samples were significantly different ( κ = −0.010 for 4-tier scoring and κ = 0.028 for dichotomized scoring) in their ezrin expression. Most preoperative biopsies (61/76, 80%) had negative/weak ezrin expression compared with 56% (43/76) of the corresponding operative samples. After preoperative treatment, negative expression in the biopsies of 18 (82%) of 22 patients turned positive, whereas positive expression in 6 (11%) of 54 biopsies turned negative in the operative samples. In univariate analysis, disease-free survival and disease-specific survival were significantly longer ( P = .027 and P = .002) when ezrin expression in the preoperative biopsy was negative/weak compared with moderate/strong expression. Such prognostic association was lost in the radiated operative specimens. In multivariate regression model, ezrin was not a predictor of disease-free survival. No direct effect of radiation on ezrin expression was seen in vitro. In conclusion, radiotherapy increases ezrin expression in rectal cancer. In pretreatment biopsies, negative/weak ezrin expression correlates with favorable disease outcome, suggesting that ezrin expression modulates tumor aggressiveness and/or response to treatment.