PMID- 38401716 OWN - NLM STAT- MEDLINE DCOM- 20240319 LR - 20240319 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 145 DP - 2024 Mar TI - DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases. PG - 56-62 LID - S0046-8177(24)00030-3 [pii] LID - 10.1016/j.humpath.2024.02.007 [doi] AB - Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Mori, Taro AU - Mori T AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Iwasaki, Takeshi AU - Iwasaki T AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Sonoda, Hiroki AU - Sonoda H AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Kawaguchi, Kengo AU - Kawaguchi K AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Tomonaga, Takumi AU - Tomonaga T AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Furukawa, Hiroshi AU - Furukawa H AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Sato, Chiaki AU - Sato C AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shiraishi, Sakura AU - Shiraishi S AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Taguchi, Kenichi AU - Taguchi K AD - Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. FAU - Tamiya, Sadafumi AU - Tamiya S AD - Department of Pathology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan. FAU - Yoneda, Reiko AU - Yoneda R AD - Department of Pathology, Hamanomachi Hospital, Fukuoka, Japan. FAU - Oshiro, Yumi AU - Oshiro Y AD - Department of Pathology, Matsuyama Red Cross Hospital, Matsuyama, Japan. FAU - Matsunobu, Tomoya AU - Matsunobu T AD - Department of Orthopaedic Surgery, Kyushu Rosai Hospital, Fukuoka, Japan. FAU - Abe, Chie AU - Abe C AD - Department of Diagnostic Pathology, Fukuokahigashi Medical Center, Fukuoka, Japan. FAU - Kuboyama, Yusuke AU - Kuboyama Y AD - Department of Pathology, Oita Red Cross Hospital, Oita, Japan. FAU - Ueki, Nozomi AU - Ueki N AD - Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. FAU - Kohashi, Kenichi AU - Kohashi K AD - Department of Humanpathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan. FAU - Yamamoto, Hidetaka AU - Yamamoto H AD - Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FAU - Nakashima, Yasuharu AU - Nakashima Y AD - Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Oda, Yoshinao AU - Oda Y AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: oda.yoshinao.389@m.kyushu-u.ac.jp. LA - eng PT - Journal Article DEP - 20240222 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (DDIT3 protein, human) RN - 147336-12-7 (Transcription Factor CHOP) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) SB - IM MH - Humans MH - *Liposarcoma/pathology MH - In Situ Hybridization, Fluorescence MH - Gene Amplification MH - *Sarcoma/genetics/pathology MH - *Lipoma/diagnosis MH - Chromosome Aberrations MH - *Soft Tissue Neoplasms/diagnosis MH - *Histiocytoma, Malignant Fibrous MH - Transcription Factor CHOP/genetics/metabolism MH - Proto-Oncogene Proteins c-mdm2/analysis OTO - NOTNLM OT - 12q13 OT - DDIT3 amplification OT - Dedifferentiated liposarcoma OT - MDM2 amplification OT - Undifferentiated pleomorphic sarcoma COIS- Declaration of competing interest The authors have no conflicts of interest to disclose. EDAT- 2024/02/25 00:42 MHDA- 2024/03/19 06:44 CRDT- 2024/02/24 19:15 PHST- 2023/11/09 00:00 [received] PHST- 2024/02/17 00:00 [revised] PHST- 2024/02/20 00:00 [accepted] PHST- 2024/03/19 06:44 [medline] PHST- 2024/02/25 00:42 [pubmed] PHST- 2024/02/24 19:15 [entrez] AID - S0046-8177(24)00030-3 [pii] AID - 10.1016/j.humpath.2024.02.007 [doi] PST - ppublish SO - Hum Pathol. 2024 Mar;145:56-62. doi: 10.1016/j.humpath.2024.02.007. Epub 2024 Feb 22.