Differential expression of retinoic acid receptors and p53 protein in normal, premalignant, and malignant esophageal tissues

Abstract

Purpose: Esophageal cancer remains a significant health problem worldwide. The very low 5-year survival rates and rapid increase in the incidence of adenocarcinoma indicate the urgent need for early identification of and new approaches to the prevention and treatment of this cancer. Methods: To find biomarkers for early identification of the disease, we analyzed nuclear retinoic retinoid receptor mRNAs, p53 protein, and the proliferation marker Ki 67 in surgical specimens of normal, mildly, and severely dysplastic and malignant esophageal tissues. Results: Nuclear retinoid receptors (RAR-α, RAR-γ, and RXR-α) were expressed in most (79%–100%) normal, dysplastic, and malignant esophageal mucosae, whereas expression of RAR-β was progressively lost from normal esophagus to carcinoma (84%–54%). In contrast, expression of p53 protein and Ki 67 were dramatically increased in severely dysplastic and cancerous tissues of the esophagus (from 5% to 62%). Conclusions: Loss of RAR-β expression and accumulation of p53 and Ki 67 proteins may serve as biomarkers for esophageal cancer.