EVALUATION OF HLA-DR EXPRESSION AND T-LYMPHOCYTE INFILTRATION IN OSTEOSARCOMA

Although in recent years the outcome of patients with osteosarcoma has considerably been improved by combining neoadjuvant chemotherapy with radical surgery, there still remains the problem of nonresponse to ch emotherapy. T-lymphocytes play a critical role in tumor immunology, an d MHC molecules are of central importance in the regulation of the imm une response. It is the aim of this study to investigate whether T-lym phocyte infiltration of osteosarcomas and HLA-DR expression on tumor c ells and infiltrating immune cells are of predicitive or diagnostic va lue. Expression of CD3, CD8 and HLA-II was evaluated immunohistochemic ally on paraffin-embedded sections of 35 patients with high-grade oste osarcoma at the time of biopsy before chemotherapy and correlated with histologic response to chemotherapy, tumor size, age, alkaline-phosph atase serum levels and duration of symptoms. Thirty-four patients with osteoblastoma (n = 7), osteoid osteoma (n = 7) or fibrous dysplasia ( n = 20) served as controls. Osteosarcomas were infiltrated by CD3(+) ( 33/35, 95%) and CD8(+) T-lymhocytes (24/35, 68%), non malignant bone t umors by CD3(+) in 91% (31/34) and CD8(+) T-lymphocytes in 74% (25/34) , respectively. T-lymphocytes were positive for HLA-DR expression in 2 9% (10/35) in ostosarcomas and in 11% (4/34) in non-malignant controls . Osteosarcoma cells were positive for HLA-DR in 11/35 (31%) and non-m alignant tumor cells in only 9% (3/34). Therefore, HLA-DR is overexpre ssed in osteosarcoma (p < 0.05). HLA-DR expression on osteosarcoma cel ls showed a positive correlation with HLA-DR expression on lymphocytes (p < 0.001) as well as with duration of symptoms and age (p < 0.05). Response to preoperative chemotherapy, gender, tumor size and serum al kaline-phosphatase levels did not correlate with the expression of the molecules tested. Our results show that HLA-DR is overexpressed in os teosarcoma cells compared to non-malignant bone-tumors. This overexpre ssion, however, fails to serve as a predictive marker for response to neoadjuvant chemotherapy. The same is also true for tumor-infiltrating lymphocytes expressing CD3, CD8 and HLA-DR. Increased HLD-DR expressi on in osteosarcoma is most likely due to the immune response against t he tumor.