Expression of cathepsin K in chordoma.

Invasive growth of chordoma is accompanied by severe destruction of adjacent bone tissue, a fact that requires high proteolytic activity at the tumor invasion fronts. In this context, cathepsin K is a candidate molecule. It is a protease with high collagenolytic and elastinolytic activity and previously thought to be restricted to osteoclasts and osteoclast-mediated bone resorption. In this study, 44 cases of chordoma of sphenooccipital localization, and 10 embryo-fetal specimens including chorda dorsalis were studied immunohistochemically for their expression of cathepsin K. In 4 additional snap-frozen chordoma cases, the enzyme expression was investigated by reverse transcription polymerase chain reaction and enzyme histochemistry. Ten chondrosarcomas of the skull base served as controls. Various concentrations of cathepsin K mRNA could be seen in all snap-frozen chordoma specimens. The protease was immunohistochemically expressed by the tumor cells. The immunoreactions were accentuated at the tumor invasion fronts. Enzyme histochemistry indicated a strong tumor cell-associated cathepsin K activity in invasive tumor components. In contrast to chordoma, cathepsin K was not significantly expressed in chorda dorsalis and chondrosarcoma of the skull base. In chondrosarcoma, protease expression was limited to osteoclastic cells localized between infiltrative tumor components and regular bone trabeculae. This study shows the significant expression and activity of cathepsin K in chordoma and implicates an important and direct role of this protease in the infiltrative growth of this tumor. This protease expression occurred during neoplastic transformation and did not appear in chorda dorsalis.