PROGNOSTIC VALUE OF DNA INDEX, S-PHASE FRACTION AND P53 PROTEIN ACCUMULATION AFTER SURGICAL RESECTION OF ESOPHAGEAL SQUAMOUS-CELL CARCINOMAS IN THAILAND

The prognostic value of cell nuclear DNA content, S-phase fraction and p53 protein accumulation in esophageal squamous-cell carcinomas was studied in a consecutive series of 80 patients from a high-incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S-phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti-p53 antibody, CO7. Biomarkers were correlated with clinico-pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymphnode status, TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S-phase fraction above 10%, aneuploidy (DNA index 1.2-1.8) and multiploidy (DNA index >2.2). This study further implicates p53 in the pathogenesis of esophageal squamous-cell carcinoma. Prognostic factors such as p53 protein, S-phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer. (C) 1995 Wiley-Liss, Inc.