PMID- 36977943
OWN - NLM
STAT- MEDLINE
DCOM- 20230609
LR  - 20230609
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 482
IP  - 6
DP  - 2023 Jun
TI  - Diagnostic value of MDM2 RNA in situ hybridization for low-grade osteosarcoma: 
      Consistency comparison of RNA in situ hybridization, fluorescence in situ 
      hybridization, and immunohistochemistry.
PG  - 999-1010
LID - 10.1007/s00428-023-03530-9 [doi]
AB  - Detection of MDM2 gene amplification via fluorescence in situ hybridization 
      (FISH) and MDM2 overexpression by immunohistochemistry (IHC) have been utilized 
      for the diagnosis of low-grade osteosarcoma (LGOS). The aim of this study was to 
      evaluate the diagnostic value of MDM2 RNA in situ hybridization (RNA-ISH) and 
      compare this assay with MDM2 FISH and IHC in distinguishing LGOS from its 
      histologic mimics. MDM2 RNA-ISH, FISH and IHC were performed on nondecalcified 
      samples of 23 LGOSs and 52 control cases. Twenty (20/21, 95.2%) LGOSs were 
      MDM2-amplified, and two cases failed in FISH. All control cases were 
      MDM2-nonamplified. All 20 MDM2-amplified LGOSs and one MDM2-nonamplified LGOS 
      harboring TP53 mutation and RB1 deletion showed positivity for RNA-ISH. Fifty of 
      the 52 (96.2%) control cases were negative for RNA-ISH. The diagnostic 
      sensitivity and specificity of MDM2 RNA-ISH were 100.0% and 96.2%, respectively. 
      Nineteen of the 23 LGOSs were evaluated by MDM2 RNA-ISH and FISH in decalcified 
      samples simultaneously. All decalcified LGOSs failed in FISH and most samples 
      (18/19) were no staining in RNA-ISH. Fifteen (15/20, 75%) MDM2-amplified LGOSs 
      were positive for IHC and 96.2% (50/52) of control cases were negative. The 
      sensitivity of RNA-ISH (100%) was higher than that of IHC (75%). In conclusion, 
      MDM2 RNA-ISH has great value for the diagnosis of LGOS, with excellent 
      consistency with FISH and better sensitivity than IHC. Acid decalcification still 
      has an adverse impact on RNA. Some MDM2-nonamplified tumors may show positivity 
      for MDM2 RNA-ISH, which needs to be analyzed comprehensively in combination with 
      clinicopathological features.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Chen, Chen
AU  - Chen C
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - He, Xin
AU  - He X
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - Chen, Min
AU  - Chen M
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - Du, Tianhai
AU  - Du T
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - Qin, Weiji
AU  - Qin W
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - Jing, Wenyi
AU  - Jing W
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China.
FAU - Zhang, Hongying
AU  - Zhang H
AUID- ORCID: 0000-0003-4748-4121
AD  - Department of Pathology, West China Hospital, Sichuan University, GuoXueXiang 37, 
      Chengdu, 610041, Sichuan, China. hy_zhang@scu.edu.cn.
LA  - eng
GR  - 81972520/National Natural Science Foundation of China/
GR  - 2018HXFH011/135 Project for Disciplines of Excellence-Clinical Research 
      Incubation Project, West China Hospital, Sichuan University/
PT  - Journal Article
DEP - 20230328
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 63231-63-0 (RNA)
RN  - 0 (Biomarkers, Tumor)
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  - RNA
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - *Osteosarcoma/diagnosis/genetics
MH  - *Bone Neoplasms/diagnosis/genetics
MH  - Biomarkers, Tumor/genetics
MH  - Proto-Oncogene Proteins c-mdm2/genetics
OTO - NOTNLM
OT  - Fluorescence in situ hybridization
OT  - Immunohistochemistry
OT  - Low-grade osteosarcoma
OT  - MDM2 amplification
OT  - RNA in situ hybridization
EDAT- 2023/03/29 06:00
MHDA- 2023/06/09 06:41
CRDT- 2023/03/28 23:29
PHST- 2022/11/21 00:00 [received]
PHST- 2023/03/17 00:00 [accepted]
PHST- 2023/01/18 00:00 [revised]
PHST- 2023/06/09 06:41 [medline]
PHST- 2023/03/29 06:00 [pubmed]
PHST- 2023/03/28 23:29 [entrez]
AID - 10.1007/s00428-023-03530-9 [pii]
AID - 10.1007/s00428-023-03530-9 [doi]
PST - ppublish
SO  - Virchows Arch. 2023 Jun;482(6):999-1010. doi: 10.1007/s00428-023-03530-9. Epub 
      2023 Mar 28.