PMID- 32815035 OWN - NLM STAT- MEDLINE DCOM- 20210330 LR - 20210330 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 478 IP - 3 DP - 2021 Mar TI - Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall. PG - 527-534 LID - 10.1007/s00428-020-02914-5 [doi] AB - 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. FAU - Tsuda, Yojiro AU - Tsuda Y AUID- ORCID: 0000-0002-4136-2601 AD - Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-Ku, Kitakyushu, 807-8555, Japan. yojiro-t@med.uoeh-u.ac.jp. FAU - Matsuyama, Atsuji AU - Matsuyama A AD - Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-Ku, Kitakyushu, 807-8555, Japan. FAU - Makihara, Kosuke AU - Makihara K AD - Department of Surgical Pathology, Kyushu Rosai Hospital, Kitakyushu, 800-0296, Japan. FAU - Higaki, Koichi AU - Higaki K AD - Division of Pathology, St Mary Hospital, Kurume, 830-8543, Japan. FAU - Motoi, Toru AU - Motoi T AD - Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 113-8677, Japan. FAU - Okuma, Tomotake AU - Okuma T AD - Department of Orthopedic Surgery and Musculoskeletal Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 113-8677, Japan. FAU - Hisaoka, Masanori AU - Hisaoka M AD - Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-Ku, Kitakyushu, 807-8555, Japan. LA - eng GR - JP18K07704/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20200820 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Biomarkers, Tumor) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (UCP1 protein, human) RN - 0 (Uncoupling Protein 1) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - EC 2.7.11.22 (CDK4 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - EC 3.4.19.12 (USP7 protein, human) RN - EC 3.4.19.12 (Ubiquitin-Specific Peptidase 7) SB - IM MH - Adipocytes/*chemistry/pathology MH - Adult MH - Aged MH - Biomarkers, Tumor/*analysis/genetics MH - Cell Nucleus/*chemistry/pathology MH - Cyclin-Dependent Kinase 4/analysis MH - Diagnosis, Differential MH - Female MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lipoma/*chemistry/genetics/pathology MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Proto-Oncogene Proteins c-mdm2/*analysis/genetics MH - Tumor Suppressor Protein p53/analysis MH - Ubiquitin-Specific Peptidase 7/analysis MH - Uncoupling Protein 1/analysis MH - Young Adult OTO - NOTNLM OT - Atypical lipomatous tumor/well differentiated liposarcoma OT - FISH OT - Hibernoma OT - Immunohistochemical pitfalls OT - MDM2 EDAT- 2020/08/21 06:00 MHDA- 2021/03/31 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/05/29 00:00 [received] PHST- 2020/08/14 00:00 [accepted] PHST- 2020/07/31 00:00 [revised] PHST- 2020/08/21 06:00 [pubmed] PHST- 2021/03/31 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1007/s00428-020-02914-5 [pii] AID - 10.1007/s00428-020-02914-5 [doi] PST - ppublish SO - Virchows Arch. 2021 Mar;478(3):527-534. doi: 10.1007/s00428-020-02914-5. Epub 2020 Aug 20.