Prognostic significance of HLA-DR antigen in dysplasia, carcinoma in situ and invasive carcinoma of the gallbladder

Abstract

Objective: Prognosis of gallbladder carcinoma is poor. The two most important factors having the greatest effect on survival are pathologic stage of disease and histologic grade of the tumour. Our study points towards the value of HLA-DR antigen in the prognosis of gallbladder carcinoma. Design: Thirty one cases of dysplasia of the gallbladder, 12 cases of carcinoma in situ, and 39 cases of invasive carcinoma for the detection of HLA-DR monoclonal antigen were studied. T helper (TH) marker (CD4) in the tumour stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. Setting: Pathology Departments of Drama General Hospital and Ippokration Hospital of Salonica in twelve years period (1990-2002). Results: HLA-DR was expressed in 20 of 31 dysplasias (64.5%), four of 12 in situ (33.3%), and in 10 of 39 invasive carcinomas (25.6%). CD4 was expressed in nine of 31, dysplasias (29%), five of 12 in situ (42%), and in 26 of 39 invasive carcincomas (67%). Conclusions: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of dysplasias, of carcinomas in situ and of invasive carcinomas agrees with the hypothesis of the dysplasia-carcinoma in situ sequence as the usual route for the development of invasive carcinoma. The immune attract mechanism by low HLA-DR signalling seems to be of minor importance in the malignant and metastatic potential of the gallbladder, epithelial tumours.