MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data.
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) may be difficult to distinguish from benign adipose tumors and from poorly differentiated sarcomas, respectively. Genetically, they are characterized by amplification of MDM2 and CDK4 genes on chromosome 12q13-15. We examined a series of 559 soft tissue tumors (44 ALT-WDLPS, 61 DDLPS, 49 benign adipose tumors, and 405 non-ALT-WDLPS/DDLPS sarcomas) for MDM2 and CDK4 expression using immunohistochemistry. MDM2 and CDK4 immunoexpressions were compared with gene amplification status (as assessed by quantitative PCR and/or comparative genomic hybridization) in 241 neoplasms. Most ALT-WDLPS/DDLPS expressed MDM2 (97%) and CDK4 (92%) as opposed to few benign adipose tumors (MDM2, 5%; CDK4, 2%) and a limited number of non-ALT-WDLSP/DDLPS sarcomas (MDM2, 19%; CDK4, 6%). The sensitivity and specificity of MDM2 and CDK4 immunostainings in identifying ALT-WDLPS/DDLPS among other soft tissue tumors were 97% and 92%, and 83% and 95%, respectively. MDM2 and CDK4 immunostainings were particularly useful to separate ALT-WDLPS from the large group of differentiated adipose tumors, and to distinguish DDLPS from poorly differentiated sarcomas. A strong correlation was observed between MDM2 and CDK4 stainings and gene amplification status. In conclusion, MDM2 and CDK4 immunostainings, which correlate with gene amplification, are helpful adjuncts to differentiate ALT-WDLPS from benign adipose tumors and to separate DDLPS from poorly differentiated sarcomas.
Binh
Matthieu Bui Nguyen
MB
Department of Pathology at the Curie Institute, Paris, France.
Sastre-Garau
Xavier
X
Guillou
Louis
L
de Pinieux
Gonzague
G
Terrier
Philippe
P
Lagacé
Réal
R
Aurias
Alain
A
Hostein
Isabelle
I
Coindre
Jean Michel
JM
D000368:Aged; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D003937:Diagnosis, Differential; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008080:Liposarcoma / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000235:genetics
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4