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

Histopathology. 2018 Jun;72(7):1145-1155. doi: 10.1111/his.13473. Epub 2018 Mar 7.

Abstract

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.

Keywords: FRS2; atypical lipomatous tumour; de-differentiated liposarcoma; fluorescence in-situ hybridisation; well-differentiated liposarcoma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cell Differentiation
  • Female
  • Gene Amplification
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / pathology
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • FRS2 protein, human
  • Membrane Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2