Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas

The aim of the present study was to characterise the ability of malignant c hondrosarcomas to invade normal bone by analysing their production of matri x metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TI MPs). For this purpose 12 chondrosarcomas were investigated for the express ion of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, an d for immunohistochemical localisation of the proteins. A characteristic fi nding of these analyses was increased expression of MMP-13, MMP-14 and TIMP -2 mRNAs in chondrosarcomas when compared with nonmalignant control samples . Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive o r have a probability of recurrence. Another finding of the present study wa s a marked heterogeneity in histologic appearance and gene expression of th e chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that a nalysis of MMPs could be a useful diagnostic indicator in patients with car tilaginous tumours and could help in differentiating between a low-grade ma lignant chondrosarcoma and a benign growing enchondroma.