HEAT-SHOCK-PROTEIN-72 EXPRESSION IN OSTEOSARCOMAS CORRELATES WITH GOOD RESPONSE TO NEOADJUVANT CHEMOTHERAPY

Although the therapeutic outcome of osteosarcoma patients has improved dramatically within the last 20 years because of combined neoadjuvant chemotherapy and surgery, the problem of drug resistance remains. Thu s far, markers that can predict the response to chemotherapy at the ti me of biopsy are not available. Heat shock proteins (hsp) 60, 72, and 73 have been shown to pig a role in tumor immunity, and our study inve stigated their expression in human osteosarcomas and nonmalignant bone tumors before neoadjuvant chemotherapy. Immunohistochemical evaluatio ns of hsp expression was performed on paraffin-embedded sections of 45 patients (17 female, 28 male, aged 6.5 to 62 years; mean, 19.4 years) with high-grade osteosarcoma at the time of biopsy, before preoperati ve chemotherapy. These results were correlated to histological respons e to chemotherapy, tumor size, age, alkaline phosphatase serum levels, and duration of symptoms. Thirty-four patients (15 male, 19 female, m ean age 27 years) with osteoblastoma, osteoid-osteoma, or fibrous dysp lasia served as nonmalignant controls. Hsp60 was uniformly found in th e cytoplasm of both benign and malignant bone tumors. Nuclear hsp73 ex pression quatitatively increased in osteosarcoma cells. Hsp72 was sign ificantly overexpressed in osteosarcomas (17 of 45, 38%) compared with nonmalignant bone tumors (1 of 34, 2.9%; P < .001). Hsp72-positive os teosarcomas responded better to neoadjuvant chemotherapy than hsp72-ne gative cases (P < .001), coexpress hsp60, and correlate with higher tu mor size (P < .005) and location in the distal femur. No differences w ere observed relative to ge, gender, duration of symptoms, alkaline ph osphatase levels, or hsp73 expression between hsp72-positive and hsp72 -negative turners. Hsp72 expression seemed to be a predictive immunohi stochemical marker for osteosarcoma, because it is the first marker to prospectively correlate to response to neoadjuvant chemotherapy. It t herefore, may be of importance in preoperative therapy regimens for no nresponding high-risk patients. Copyright (C) 1998 by W.B. Saunders Co mpany.