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.
Fluorescence in situ hybridization
Immunohistochemistry
Low-grade osteosarcoma
MDM2 amplification
RNA in situ hybridization
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
21
11
2022
accepted:
17
03
2023
revised:
18
01
2023
medline:
9
6
2023
pubmed:
29
3
2023
entrez:
28
3
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36977943
doi: 10.1007/s00428-023-03530-9
pii: 10.1007/s00428-023-03530-9
doi:
Substances chimiques
RNA
63231-63-0
Biomarkers, Tumor
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
999-1010Subventions
Organisme : National Natural Science Foundation of China
ID : 81972520
Organisme : 135 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University
ID : 2018HXFH011
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Hang JF, Chen PC (2014) Parosteal osteosarcoma. Arch Pathol Lab Med 138:694–699. https://doi.org/10.5858/arpa.2013-0030-RS
doi: 10.5858/arpa.2013-0030-RS
pubmed: 24786129
Schwab JH, Antonescu CR, Athanasian EA, Boland PJ, Healey JH, Morris CD (2008) A comparison of intramedullary and juxtacortical low-grade osteogenic sarcoma. Clin Orthop Relat Res 466:1318–1322. https://doi.org/10.1007/s11999-008-0251-2
doi: 10.1007/s11999-008-0251-2
pubmed: 18425560
pmcid: 2384019
Antonescu CR, Blay J-Y, Bovee JVMG, Bridge JA, Cunha IW, Dei Tos AP, Flanagan AM, Fletcher CDM, Folpe A, Hornick JL, Mertens F, Miettinen M, Nielsen GP, Oda Y, Yoshida A (2020) World Health Organization classification of tumours of soft tissue and bone, 5th edn. IARC Press, Lyon
Kurt AM, Unni KK, McLeod RA, Pritchard DJ (1990) Low-grade intraosseous osteosarcoma. Cancer 65:1418–1428. https://doi.org/10.1002/1097-0142(19900315)65:6%3c1418::aid-cncr2820650629%3e3.0.co;2-q
doi: 10.1002/1097-0142(19900315)65:6<1418::aid-cncr2820650629>3.0.co;2-q
pubmed: 2306687
Duhamel LA, Ye H, Halai D, Idowu BD, Presneau N, Tirabosco R, Flanagan AM (2012) Frequency of Mouse Double Minute 2 (MDM2) and Mouse Double Minute 4 (MDM4) amplification in parosteal and conventional osteosarcoma subtypes. Histopathology 60:357–359. https://doi.org/10.1111/j.1365-2559.2011.04023.x
doi: 10.1111/j.1365-2559.2011.04023.x
pubmed: 22074548
Dujardin F, Binh MB, Bouvier C, Gomez-Brouchet A, Larousserie F, Muret A, Louis-Brennetot C, Aurias A, Coindre JM, Guillou L, Pedeutour F, Duval H, Collin C, de Pinieux G (2011) MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone. Mod Pathol 24:624–637. https://doi.org/10.1038/modpathol.2010.229
doi: 10.1038/modpathol.2010.229
pubmed: 21336260
Mejia-Guerrero S, Quejada M, Gokgoz N, Gill M, Parkes RK, Wunder JS, Andrulis IL (2010) Characterization of the 12q15 MDM2 and 12q13–14 CDK4 amplicons and clinical correlations in osteosarcoma. Genes Chromosomes Cancer 49:518–525 https://doi.org/10.1002/gcc.20761
He X, Pang Z, Zhang X, Lan T, Chen H, Chen M, Yang H, Huang J, Chen Y, Zhang Z, Jing W, Peng R, Zhang H (2018) Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis. Am J Surg Pathol 42:1143–1155. https://doi.org/10.1097/pas.0000000000001125
doi: 10.1097/pas.0000000000001125
pubmed: 30001240
Miquelestorena-Standley E, Jourdan ML, Collin C, Bouvier C, Larousserie F, Aubert S, Gomez-Brouchet A, Guinebretière JM, Tallegas M, Brulin B, Le Nail LR, Tallet A, Le Loarer F, Massiere J, Galant C, de Pinieux G (2020) Effect of decalcification protocols on immunohistochemistry and molecular analyses of bone samples. Mod Pathol 33:1505–1517. https://doi.org/10.1038/s41379-020-0503-6
doi: 10.1038/s41379-020-0503-6
pubmed: 32094425
Mueller C, Gambarotti M, Benini S, Picci P, Righi A, Stevanin M, Hombach-Klonisch S, Henderson D, Liotta L, Espina V (2019) Unlocking bone for proteomic analysis and FISH. Lab Invest 99:708–721. https://doi.org/10.1038/s41374-018-0168-7
doi: 10.1038/s41374-018-0168-7
pubmed: 30659273
Limbach AL, Lingen MW, McElherne J, Mashek H, Fitzpatrick C, Hyjek E, Mostofi R, Cipriani NA (2020) The Utility of MDM2 and CDK4 Immunohistochemistry and MDM2 FISH in Craniofacial Osteosarcoma. Head Neck Pathol 14:889–898. https://doi.org/10.1007/s12105-020-01139-x
doi: 10.1007/s12105-020-01139-x
pubmed: 32026294
pmcid: 7669933
Yoshida A, Ushiku T, Motoi T, Shibata T, Beppu Y, Fukayama M, Tsuda H (2010) Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics. Mod Pathol 23:1279–1288. https://doi.org/10.1038/modpathol.2010.124
doi: 10.1038/modpathol.2010.124
pubmed: 20601938
Wang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A, Wu X, Vo HT, Ma XJ, Luo Y (2012) RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn 14:22–29. https://doi.org/10.1016/j.jmoldx.2011.08.002
doi: 10.1016/j.jmoldx.2011.08.002
pubmed: 22166544
pmcid: 3338343
Kulkarni AS, Wojcik JB, Chougule A, Arora K, Chittampalli Y, Kurzawa P, Mullen JT, Chebib I, Nielsen GP, Rivera MN, Ting DT, Deshpande V (2019) MDM2 RNA In Situ Hybridization for the Diagnosis of Atypical Lipomatous Tumor: A Study Evaluating DNA, RNA, and Protein Expression. Am J Surg Pathol 43:446–454. https://doi.org/10.1097/pas.0000000000001199
doi: 10.1097/pas.0000000000001199
pubmed: 30520819
Hung YP, Michal M, Dubuc AM, Rosenberg AE, Nielsen GP (2020) Dysplastic lipoma: potential diagnostic pitfall of using MDM2 RNA in situ hybridization to distinguish between lipoma and atypical lipomatous tumor. Hum Pathol 101:53–57. https://doi.org/10.1016/j.humpath.2020.05.004
doi: 10.1016/j.humpath.2020.05.004
pubmed: 32439322
Zhang H, Bu H, Chen H, Wei B, Liu W, Guo J, Li F, Liao D, Tang Y, Zhang Z (2008) Comparison of immunohistochemical markers in the differential diagnosis of adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors. Appl Immunohistochem Mol Morphol 16:32–39. https://doi.org/10.1097/PAI.0b013e318032cf56
doi: 10.1097/PAI.0b013e318032cf56
pubmed: 18091323
Zhang H, Erickson-Johnson M, Wang X, Oliveira JL, Nascimento AG, Sim FH, Wenger DE, Zamolyi RQ, Pannain VL, Oliveira AM (2010) Molecular testing for lipomatous tumors: critical analysis and test recommendations based on the analysis of 405 extremity-based tumors. Am J Surg Pathol 34:1304–1311. https://doi.org/10.1097/PAS.0b013e3181e92d0b
doi: 10.1097/PAS.0b013e3181e92d0b
pubmed: 20679883
Weaver J, Downs-Kelly E, Goldblum JR, Turner S, Kulkarni S, Tubbs RR, Rubin BP, Skacel M (2008) Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol 21:943–949. https://doi.org/10.1038/modpathol.2008.84
doi: 10.1038/modpathol.2008.84
pubmed: 18500263
Touqan N, Diggle CP, Verghese ET, Perry S, Horgan K, Merchant W, Anwar R, Markham AF, Carr IM, Achuthan R (2013) An observational study on the expression levels of MDM2 and MDMX proteins, and associated effects on P53 in a series of human liposarcomas. BMC Clin Pathol 13:32. https://doi.org/10.1186/1472-6890-13-32
doi: 10.1186/1472-6890-13-32
pubmed: 24330579
pmcid: 4028812
Chen CY, Zhang HZ, Jiang ZM, Zhou J, Chen J, Liu L (2016) Value of MDM2, CDK4 and SATB2 immunohistochemistry in histologic diagnosis of low-grade osteosarcoma. Zhonghua Bing Li Xue Za Zhi 45:387–392. https://doi.org/10.3760/cma.j.issn.0529-5807.2016.06.007
doi: 10.3760/cma.j.issn.0529-5807.2016.06.007
pubmed: 27256046
Yoshida A, Ushiku T, Motoi T, Beppu Y, Fukayama M, Tsuda H, Shibata T (2012) MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype. Am J Surg Pathol 36:423–431. https://doi.org/10.1097/PAS.0b013e31824230d0
doi: 10.1097/PAS.0b013e31824230d0
pubmed: 22301501
Anderson CM, Zhang B, Miller M, Butko E, Wu X, Laver T, Kernag C, Kim J, Luo Y, Lamparski H, Park E, Su N, Ma XJ (2016) Fully Automated RNAscope In Situ Hybridization Assays for Formalin-Fixed Paraffin-Embedded Cells and Tissues. J Cell Biochem 117:2201–2208. https://doi.org/10.1002/jcb.25606
doi: 10.1002/jcb.25606
pubmed: 27191821
pmcid: 5132049
Choi SE, Hong SW, Yoon SO (2015) Proposal of an appropriate decalcification method of bone marrow biopsy specimens in the era of expanding genetic molecular study. J Pathol Transl Med 49:236–242. https://doi.org/10.4132/jptm.2015.03.16
doi: 10.4132/jptm.2015.03.16
pubmed: 26018515
pmcid: 4440935
Flørenes VA, Maelandsmo GM, Forus A, Andreassen A, Myklebost O, Fodstad O (1994) MDM2 gene amplification and transcript levels in human sarcomas: relationship to TP53 gene status. J Natl Cancer Inst 86:1297–1302. https://doi.org/10.1093/jnci/86.17.1297
doi: 10.1093/jnci/86.17.1297
pubmed: 8064888
Jiao YF, Nakamura S, Sugai T, Habano W, Uesugi N, Oikawa M, Sato T (2002) p53 gene mutation and MDM2 overexpression in a case of primary malignant fibrous histiocytoma of the jejunum. APMIS 110:165–171. https://doi.org/10.1034/j.1600-0463.2002.100207.x
doi: 10.1034/j.1600-0463.2002.100207.x
pubmed: 12064872
Meltzer PS (1994) MDM2 and p53: a question of balance. J Natl Cancer Inst 86:1265–1266. https://doi.org/10.1093/jnci/86.17.1265
doi: 10.1093/jnci/86.17.1265
pubmed: 8064885
Peng Y, Chen L, Li C, Lu W, Agrawal S, Chen J (2001) Stabilization of the MDM2 oncoprotein by mutant p53. J Biol Chem 276:6874–6878. https://doi.org/10.1074/jbc.C000781200
doi: 10.1074/jbc.C000781200
pubmed: 11152666
Lianes P, Orlow I, Zhang ZF, Oliva MR, Sarkis AS, Reuter VE, Cordon-Cardo C (1994) Altered patterns of MDM2 and TP53 expression in human bladder cancer. J Natl Cancer Inst 86:1325–1330. https://doi.org/10.1093/jnci/86.17.1325
doi: 10.1093/jnci/86.17.1325
pubmed: 8064890
Bouska A, Lushnikova T, Plaza S, Eischen CM (2008) MDM2 promotes genetic instability and transformation independent of p53. Mol Cell Biol 28:4862–4874. https://doi.org/10.1128/mcb.01584-07
doi: 10.1128/mcb.01584-07
pubmed: 18541670
pmcid: 2493369
Pan Y, Haines DS (2000) Identification of a tumor-derived p53 mutant with novel transactivating selectivity. Oncogene 19:3095–3100. https://doi.org/10.1038/sj.onc.1203663
doi: 10.1038/sj.onc.1203663
pubmed: 10871862
Simons A, Schepens M, Jeuken J, Sprenger S, van de Zande G, Bjerkehagen B, Forus A, Weibolt V, Molenaar I, van den Berg E, Myklebost O, Bridge J, van Kessel AG, Suijkerbuijk R (2000) Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma. Cancer Genet Cytogenet 118:89–98. https://doi.org/10.1016/s0165-4608(99)00178-8
doi: 10.1016/s0165-4608(99)00178-8
pubmed: 10748288