OSTEOSARCOMA ONCOGENE EXPRESSION DETECTED BY IN-SITU HYBRIDIZATION

Fifteen archival human osteosarcoma specimens were examined by in situ hybridization for the expression of human and mouse transforming grow th factor-beta (isoforms 1, 2, and 3), c-fos, and metalloproteinase (s tromelysin-3 and matrilysin). Osteosarcoma subtypes were confirmed by review of patients' radiographs, histopathology, and age at diagnosis. The outcome and method of treatment were documented. The subtypes of osteosarcoma consisted of nine conventional osteosarcomas and two each of fibroblastic, telangiectatic, and post-radiation osteosarcomas. Ea ch specimen was histologically examined under light microscopy, and th en adjacent paraffin sections were assayed with sense and anti-sense R NA probes by in situ hybridization. The probes localized to the neopla stic cells, confirming the methodology of the technique. Human transfo rming growth factor-beta 1 had the most uniform binding affinity to th e osteosarcomas examined and was more specific in binding than mouse t ransforming growth factor-beta 1. Specific mRNA encoding for the trans forming growth factor-beta s, c-fos, and metalloproteinases are detect able in patterns within osteosarcoma cells, and collectively, their ex pression parallels the different histopathologic subtypes. The less di fferentiated subtypes (telangiectatic and post-radiation osteosarcomas ) expressed the fewest molecular markers. Osteosarcoma is a heterogene ous tumor. Differential expression of matrilysin in osteosarcoma is th e first reported detection of metalloproteinase activity in human skel etal sarcoma.