The number of nucleolar organizer region proteins identified by silver staining (AgNORs) and alterations in cell surface glycoproteins identified by Helix pomatia agglutinin (HPA) immunostaining were studied in 96 primary esophageal carcinomas. The number of AgNORs increased with increasing depth of cancer invasion, venous involvement, lymphatic invasion, and tumor stage. Positivity of HPA staining correlated significantly with increasing depth of cancer invasion, venous invasion, and tumor stage. Forty of 42 HPA negative cases had low AgNORs numbers (< 4), while 39 of 54 HPA positive cases had high AgNORs numbers (> or = 4) (P = 0.0001). The survival rate of patients with stage III and IV disease was significantly poorer for those with a high AgNORs score and HPA positivity than in those with a low AgNORs score and HPA negativity. The present study indicates that the AgNORs score is positively correlated with positive HPA staining and that tumors having both factors represent a subgroup of esophageal carcinomas with poor prognosis.