Abl expression, tumour grade, and apoptosis in chondrosarcoma

Aims-To determine whether Abl immunoreactivity correlates with grade and ce ll kinetics (apoptosis and mitosis) in chondrosarcoma. Methods-Sections from 16 chondrosarcomas were stained immunohistochemically using a polyclonal antibody to the c-Abl/Bcr-Abl oncoprotein. Apoptotic in dices and mitotic indices were assessed in all tumours. Sections from 24 pa raffin wax blocks of human fetal rib (gestational ages, 15-42 weeks) were a lso stained to determine whether the Abl protein is synthesised consistentl y throughout endochondral ossification. Results-Abl staining in immature fetal rib chondrocytes at all stages of de velopment was predominantly nuclear, and 70% of cells showed moderate to st rong staining. Abl immunoreactivity was minimal or absent in hypertrophic c hondrocytes about to undergo apoptosis at the growth plate. There was stron g Abl staining in grade 1 and grade 2 chondrosarcomas but staining was grea tly reduced or absent in grade 3 chondrosarcomas. There was a very signific ant linear correlation between apoptotic index (mean, 0.68%; range, 0-3.2%) and mitotic index (mean, 0.23%; range, 0-0.9%), and both indices were sign ificantly lower in grade 1 than in grade 2 and grade 3 chondrosarcomas. Conclusions-These data suggest that abl gene expression is associated with differentiation and apoptosis inhibition in fetal and neoplastic chondrocyt es. However, these putative effects cannot be ascribed solely to the Abl pr otein, because several additional factors contribute to the regulation of b oth differentiation and apoptosis.