Clinico-pathologic and molecular analysis of myxofibrosarcoma of the extremities.

AIM The aim of this study was to perform a molecular analysis and to identify class of risk, in terms of local recurrence and survival, in patients affected by myxofibrosarcoma (MFS) of the extremities. MATERIALS AND METHODS A total of 166 patients (>18 years) affected by primary MFS of the extremities were included. Immunohistochemistry expression of MET, RET, p53 and Rb1 was evaluated on tissue MicroArray (TMA) in the whole series. Next generation sequencing (NGS) analysis was performed on 20 samples. Differences in p53 mutations were observed among relapsed and not relapsed cases. Thus, Sanger sequencing was performed on a total of 83 samples. Somatic copy number variations (CNV) of analyzed genes were hypothesized based on allelic frequencies observed. A digital assay of p53 and Met was therefore performed to confirm and characterize them as amplifications or deletions. RESULTS HIC was positive for MET protein in 81.9% and positive for p53 in 19.3%. Point mutations in Tp53 were observed in 25.3%.ses. Point mutations alone were observed in only two cases (2.3%), whereas in 19 (22.9%) they were associated with a gene deletion. Most of the cases (52, 61.9%) presented a Tp53 gene deletion. Cases with overexpression of MET had a higher risk of local recurrence (LR) (p=0.047), Tp53 point mutations increased the risk of LR (p=0.032). CONCLUSIONS We confirm that Tp53 and MET are frequently altered genes in MFS of the extremities. Both CNV and point mutations appear to play important roles in MFS tumorigenesis. Point mutations in Tp53 seem to influence the risk of both local recurrence and survival.