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Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall

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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.

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All data generated or analyzed during this study are included in this published article.

Funding

This study was partially funded by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (KAKENHI) (grant number JP18K07704).

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All authors read and approved the final manuscript. Yojiro Tsuda is responsible for data curation, investigation, writing—original draft, and writing—review and editing. Atsuji Matsuyama is responsible for methodology and investigation. Koichi Higaki, Toru Motoi, Kosuke Makihara, and Tomotake Okuma are responsible for investigation and resources. Masanori Hisaoka is responsible for conceptualization, methodology, and supervision.

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Correspondence to Yojiro Tsuda.

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The Ethics Committee of Medical Research, University of Occupational and Environmental Health, Japan approved this study (No. H25-169).

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Tsuda, Y., Matsuyama, A., Makihara, K. et al. Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall. Virchows Arch 478, 527–534 (2021). https://doi.org/10.1007/s00428-020-02914-5

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  • DOI: https://doi.org/10.1007/s00428-020-02914-5

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