Major histocompatibility complex molecules (HLA), the co-stimulatory molecule B7 and the intercellular adhesion molecule 1 (ICAM-1) are key molecules involved in T cell-mediated immune surveillance. We aimed at assessing the expression pattern of these immunoregulatory molecules on primary esophageal carcinomas and evaluating their prognostic significance. Representative samples of primary tumors were obtained from 53 patients who had undergone radical en bloc esophagectomy without residual tumor. Cryostat sections of these tumors were stained with monoclonal antibodies (MAbs) directed against either HLA class I, HLA class II, B7 or ICAM-1. The median follow-up was 19 months (range, 6-43). We found that HLA class I expression was deficient on 27 tumors, while a significant neo-expression of HLA class II, B7 and ICAM-1 (> or =25% positive tumor cells) was observed on 17, 29 and 25, tumors, respectively. Kaplan-Meier analyses revealed a significant beneficial influence on relapse-free survival for patients with tumors expressing HLA class I, HLA class II and B7. Cox's regression analyses demonstrated that co-expression of HLA class I and ICAM-1 was a significant and independent predictor of a reduced risk of developing tumor recurrence, whereas expression of ICAM-1 on HLA class I negative tumors was correlated with an increased risk of tumor relapse.