title: Preoperative radiotherapy modulates ezrin expression and its value as a predictive marker in patients with rectal cancer.
abstract: 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.
authors.affiliation: Department of Oncology and Radiotherapy, University of Turku, Turku University Hospital, Hämeentie 11, PB 52, FIN-20521 Turku, Finland. eija.korkeila@tyks.fi
authors.forename: Eija A
authors.initials: EA
authors.lastname: Korkeila
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.forename: Riyad
authors.initials: R
authors.lastname: Bendardaf
authors.forename: Minja
authors.initials: M
authors.lastname: Laulajainen
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
authors.forename: Jari
authors.initials: J
authors.lastname: Sundström
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011300:Preoperative Care; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013997:Time Factors; D000099149:Ezrin
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D000099149:Ezrin