Loss of HLA class I antigen expression on disseminated tumor cells in bonemarrow of breast cancer patients relates to poor prognosis

Background: Not only presence or abscense of micrometastatic cells in bone marrow, but also a certain phenotype of these cells might be relevant for t he prognosis of the patients. As histocompatibility antigens are involved i n the mechanism of immunsurveilance, this study investigated HLA-dass I ant igen expression pattern on disseminated tumor cells in breast cancer patien ts and its prognostic impact. Methods: A double staining procedure combining APAAP staining and immunogol d labelling was applied using the monoclonal antibodies CK2 and W6/32. 1 x 10(6) cells per patient were analysed after intraoperative bone marrow aspi ration. Slights were examined under light microscopy by two independent obs ervers. Results and Conclusion: 35 breast cancer patients with CK2 positive cells i n bone marrow were analysed for HLA class I antigen expression using mab W6 /32. In 57.1% of the cases all disseminated cells were W6/32 positive and 4 2.9% of the patients revealed a partiell or complete loss of HLA class I an tigen expression on micrometastatic cells in bone marrow. In univariate ana lyses this corresponds to poor survival in patients with a loss of HLA clas s I antigen expression (Kaplan Meier log rang p less than or equal to 0.05; median follow-up 26.4 month). Several studies revealed an unfavourable pro gnostic impact of loss of HLA class I antigen expression in various primary tumours. This is the first study demonstrating a possible prognostic impac t also for minimal residual disease. Therapeutic strategies aiming at upreg ulation of HLA-class I antigen expression might be useful in this situation .