Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall.

Abstract

Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.

• Authors: Yojiro Tsuda, Atsuji Matsuyama, Kosuke Makihara, Koichi Higaki, Toru Motoi, Tomotake Okuma, Masanori Hisaoka
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 478 Issue 3 Pg. 527-534 (Mar 2021) ISSN: 1432-2307 [Electronic] Germany
• PMID: 32815035 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• TP53 protein, human
• Tumor Suppressor Protein p53
• UCP1 protein, human
• Uncoupling Protein 1
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2
• CDK4 protein, human
• Cyclin-Dependent Kinase 4
• USP7 protein, human
• Ubiquitin-Specific Peptidase 7

Topics

• Adipocytes (chemistry, pathology)
• Adult
• Aged
• Biomarkers, Tumor (analysis, genetics)
• Cell Nucleus (chemistry, pathology)
• Cyclin-Dependent Kinase 4 (analysis)
• Diagnosis, Differential
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Lipoma (chemistry, genetics, pathology)
• Male
• Middle Aged
• Predictive Value of Tests
• Proto-Oncogene Proteins c-mdm2 (analysis, genetics)
• Tumor Suppressor Protein p53 (analysis)
• Ubiquitin-Specific Peptidase 7 (analysis)
• Uncoupling Protein 1 (analysis)
• Young Adult