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Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 9...

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Autores principales: Wągrodzki, Michał, Tysarowski, Andrzej, Seliga, Katarzyna, Wojnowska, Aneta, Stepaniuk, Maria, Castañeda Wysocka, Patrycja, Makuła, Donata, Pieńkowski, Andrzej, Szostakowski, Bartłomiej, Zub, Renata, Rutkowski, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778699/
https://www.ncbi.nlm.nih.gov/pubmed/35055156
http://dx.doi.org/10.3390/ijms23020969
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author Wągrodzki, Michał
Tysarowski, Andrzej
Seliga, Katarzyna
Wojnowska, Aneta
Stepaniuk, Maria
Castañeda Wysocka, Patrycja
Makuła, Donata
Pieńkowski, Andrzej
Szostakowski, Bartłomiej
Zub, Renata
Rutkowski, Piotr
author_facet Wągrodzki, Michał
Tysarowski, Andrzej
Seliga, Katarzyna
Wojnowska, Aneta
Stepaniuk, Maria
Castañeda Wysocka, Patrycja
Makuła, Donata
Pieńkowski, Andrzej
Szostakowski, Bartłomiej
Zub, Renata
Rutkowski, Piotr
author_sort Wągrodzki, Michał
collection PubMed
description To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.
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spelling pubmed-87786992022-01-22 Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone Wągrodzki, Michał Tysarowski, Andrzej Seliga, Katarzyna Wojnowska, Aneta Stepaniuk, Maria Castañeda Wysocka, Patrycja Makuła, Donata Pieńkowski, Andrzej Szostakowski, Bartłomiej Zub, Renata Rutkowski, Piotr Int J Mol Sci Article To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB. MDPI 2022-01-16 /pmc/articles/PMC8778699/ /pubmed/35055156 http://dx.doi.org/10.3390/ijms23020969 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wągrodzki, Michał
Tysarowski, Andrzej
Seliga, Katarzyna
Wojnowska, Aneta
Stepaniuk, Maria
Castañeda Wysocka, Patrycja
Makuła, Donata
Pieńkowski, Andrzej
Szostakowski, Bartłomiej
Zub, Renata
Rutkowski, Piotr
Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title_full Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title_fullStr Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title_full_unstemmed Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title_short Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
title_sort diagnostic utility of genetic and immunohistochemical h3-3a mutation analysis in giant cell tumour of bone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778699/
https://www.ncbi.nlm.nih.gov/pubmed/35055156
http://dx.doi.org/10.3390/ijms23020969
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