CDNA ARRAY BASED ANALYSIS OF THE GENE EXPRESSION OF CHONDROSARCOMA OF DIFFERENT HISTOLOGICAL GRADES (EORS Award Finalist 2008)

Abstract

Chondrosarcomas are hyaline cartilage-forming tumours which can be classified according to malignancy through histological grading. Grade I chondrosarcomas rarely metastasize whereas in grade III chondrosarcoma metastasis is observed in 71% of cases. There is, so far, no clear molecular marker allowing an objective classification of chondrosarcoma. The aim of this project was to identify such marker genes through the comparison of gene expression of chondrosarcoma and normal hyaline cartilage and through the correlation of expression profiles to histological grading.

The mRNA of 19 chondrosarcomas with different histological grades and of eight normal cartilage samples was analysed. Gene expression profiles were assessed on a customised cDNA array including 230 cartilage- and stem cell-relevant genes. Data were analysed by hierarchical clustering and significance analysis of microarrays. Results were confirmed by real-time RT-PCR.

Gene expression profiles clearly discriminated between normal and neoplastic cartilage. Between them, 73 differentially expressed genes were identified. The genes higher expressed in cartilage included several genes encoding matrix proteins. Among the genes higher expressed in chondrosarcoma, molecules involved in PTH and BMP signalling were found. Genes differentially expressed between tumours of different grade were identified. Among others, galectin 1 was significantly higher expressed in highly malignant tumours compared to grade I tumours. This correlation could be confirmed at protein level by immunohistological analysis.

The comparative analysis of normal cartilage and chondrosarcoma gene expression showed that there are important molecular differences between the matrix of normal and neoplastic cartilage. Our results furthermore confirm that genes implicated in the regulation of the growth plate were expressed in chondrosarcoma. Remarkably, we identified galectin 1 as a marker correlating to malignancy on the level of gene and protein expression. More extended studies on this functionally polyvalent molecule would be necessary to establish it as a marker for malignancy in chondrosarcoma.