Immunohistochemical Analysis of Expression of RB1, CDK4, CHMP2B, cPLA2G4A and HSP90 in Myxofibrosarcoma and Myxoid Liposarcoma
Tao Wang, Richard L McGough, Mark A Goodman, Kurt R Weiss, Uma NM Rao. University Pittsburgh of Medical Center, Pittsburgh, PA; University Pittsburgh of Medical Center, Shadyside Hospital, Pittsburgh, PA
Background: Distinction of myxofibrosarcoma from myxoid liposarcoma can be difficult because of overlapping morphological patterns. This study addresses the diagnostic efficacy and possible role of gene products that have been shown to display varied cellular functions in liposarcoma and other tumors. Cell cycle regulators RB1 and CDK4 are overexpressed in well-differentiated and dedifferentiated liposarcoma. CHMP2B is a core component of endosomal sorting complex required for transport (ESCRT-III) that has been shown to be implicated in myxofibrosarcoma and dedifferentiated liposarcoma. cPLA2G4A belongs to group IV phospholipase A2 family and contributes to tumor progression and angiogenesis in some epithelial neoplasia. HSP90 is a molecular chaperone involved in signal transduction, protein folding, and conformation.
Design: Formalin fixed paraffin blocks from 32 myxofibrosarcoma patients and 29 myxoid liposarcoma patients were accrued following approval by our IRB. All initial diagnosis were confirmed by fluorescence in situ hybridization for CHOP. Immunohistochemical stains for RB1, CDK4, CHMP2B, HSP90 and cPLA2G4A were performed on each case with appropriate negative and positive controls. Only tumors with moderate to strong nuclear and /or cytoplasmic positivity in greater than 30% of the tumor cells were evaluated.
Results: HSP90 demonstrated strong nuclear stain in all liposarcoma cases. Only 4 myxofibrosarcomas showed scattered positivity for HSP90. All but 4 cases of myxofibrosarcoma displayed strong diffuse or focal positivity for cPLA2G4A and CHMP2B stains. In myxoid liposarcoma, cPLA2G4A was positive in only 2 cases with round cell component and both were CHMP2B negative. 8 out of 29 myxoid liposarcoma cases were positive for CDK4, while 15 out of 32 myxofibrosarcoma cases were CDK4 positive. All cases, including high grade tumors, were negative for RB1.
Conclusions: HSP90 and cPLA2G4A may be useful in distinguishing myxofibrosarcoma from myxoid liposarcoma (sensitivity = 100% and 81.3%, specificity = 87.5% and 93.1%, p<0.00000001 and =0.00000001, respectively). There is loss of RB1 and compensatory CDK4 expression in both myxoid liposarcoma and myxofibrosarcoma. Overexpression of cPLA2G4A or CHMP2B could indicate high grade tumor (p=0.044) and are perhaps involved with tumor progression. cPLA2G4A, HSP90 and CHMP2B may also represent potential molecular targets for novel therapeutic approaches.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 28, Monday Afternoon