Amplification of FRS2 in Atypical Lipomatous Tumour/well-differentiated Liposarcoma and De-differentiated Liposarcoma: a Clinicopathological and Genetic Study of 146 Cases

Aims: The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL)/de-differentiated liposarcoma (DDL).

Methods And Results: FRS2 and MDM2 fluorescence in-situ hybridisation (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs). One hundred and eight control samples were included for FRS2 analysis. FRS2 amplification was detected in 136 of 146 (93.2%) ALT/WDL/DDLs, including 63 ALT/WDLs and 73 DDLs. A higher FRS2/CEP12 ratio was observed in DDLs than in ALT/WDLs (P = 0.0005). The FRS2/CEP12 ratio of peripheral tumours was lower than that of central tumours (P = 0.00004). All the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2 /FRS2 series included seven ALT/WDLs and three DDLs. Four of seven (57.1%) MDM2 /FRS2 ALT/WDLs occurred in peripheral sites, slightly higher than the percentage of MDM2 /FRS2 ALT/WDLs (28 of 63, 44.4%). All the three MDM2 /FRS2 DDLs (100%) were peripheral tumours, a much higher proportion than that of MDM2 /FRS2 DDLs (10 of 73, 13.7%). A high percentage of homologous pleomorphic liposarcoma-like DDLs (two of three) were observed in the MDM2 /FRS2 group. In the control group all the parosteal osteosarcomas (five of five, 100%) were FRS2 amplified, whereas the remaining 103 samples were FRS2 non-amplified.

Conclusions: These findings suggest that FRS2 is amplified consistently in ALT/WDL/DDLs and offer another avenue for the investigation of the biology of this tumour group. MDM2 /FRS2 cases seem to be associated with certain clinicopathological features, and further investigation is needed.