MOLECULAR MARKERS IN OSTEOSARCOMA – A cDNA MICROARRAY AND RT-PCR ANALYSIS

Abstract

Osteosarcomas account for about 20% of all primary bone neoplasms, and affect predominantly adolescents. Important prognostic factors include the presence or absence of metastases at the time of presentation and tumor response to neoadjuvant chemotherapy. Biological markers predicting metastases and chemoresistance are not well characterized. cDNA microarray analysis enables one to examine the expression of thousands of genes in tumor samples. We performed cDNA microarray analysis of histologically low and high grade areas in osteosarcomas to identify gene expression patterns which may depict aggressive behavior. Microarray analysis with 1.2 K cancer array revealed many differentially expressed genes (both upregulated and downregulated), in histologically high grade tumor samples as compared with a low grade sample. Selected up and down regulated markers in the high grade sarcomas were tested in a group of high grade osteosarcomnas (OS) with varying responses to chemotherapy. Of the multiple markers analyzed, ezrin, a member of the ERM family of membrane-cytoskeleton linkers showed an expression pattern statistically significant between tumors with good response to chemotherapy compared with tumors with poor response (p = 0.036). We discuss our findings, with current review of literature.