Amplification of FRS2 in atypical lipomatous tumour/well -differentiated liposarcoma and dedifferentiated liposarcoma: a clinicopathological and genetic study of 146 cases

Abstract

Aims

Fibroblast growth factor receptor substrate 2 (FRS2) is located within the 12q13-15 band. 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)/dedifferentiated liposarcoma (DDL).

Methods and results

FRS2 and MDM2 fluorescence in situ hybridization (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 of the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2+/FRS2- series included 7 ALT/WDLs and 3 DDLs. Four of 7 (57.1%) MDM2+/FRS2- ALT/WDLs occurred in peripheral sites, slightly higher than the percentage of MDM2+/FRS2+ ALT/WDLs (28/63, 44.4%). All of the 3 MDM2+/FRS2- DDLs (100%) were peripheral tumours, a much higher proportion than that of MDM2+/FRS2+ DDLs (10/73, 13.7%). A high percentage of homologous pleomorphic liposarcoma-like DDLs (2/3) were observed in the MDM2+/FRS2- group. In the control group, all of the parosteal osteosarcomas (5/5, 100%) were FRS2-amplified, whereas the remaining 103 samples were FRS2-nonamplified.

Conclusions

These findings suggest that FRS2 is consistently amplified 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.

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