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p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer

High-grade serous carcinoma (HGSCa) of the ovary is featured by TP53 gene mutation. Missense or nonsense mutation types accompany most cases of HGSCa that correlate well with immunohistochemical (IHC) staining results—an all (missense) or none (nonsense) pattern. However, some IHCs produce subclonal...

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Autores principales: Park, Eunhyang, Han, Hyunho, Choi, Sung-Eun, Park, Hyunjin, Woo, Ha-Young, Jang, Mi, Shim, Hyo-Sup, Hwang, Sohyun, Kang, Haeyoun, Cho, Nam-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947437/
https://www.ncbi.nlm.nih.gov/pubmed/35328131
http://dx.doi.org/10.3390/diagnostics12030579
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author Park, Eunhyang
Han, Hyunho
Choi, Sung-Eun
Park, Hyunjin
Woo, Ha-Young
Jang, Mi
Shim, Hyo-Sup
Hwang, Sohyun
Kang, Haeyoun
Cho, Nam-Hoon
author_facet Park, Eunhyang
Han, Hyunho
Choi, Sung-Eun
Park, Hyunjin
Woo, Ha-Young
Jang, Mi
Shim, Hyo-Sup
Hwang, Sohyun
Kang, Haeyoun
Cho, Nam-Hoon
author_sort Park, Eunhyang
collection PubMed
description High-grade serous carcinoma (HGSCa) of the ovary is featured by TP53 gene mutation. Missense or nonsense mutation types accompany most cases of HGSCa that correlate well with immunohistochemical (IHC) staining results—an all (missense) or none (nonsense) pattern. However, some IHCs produce subclonal or mosaic patterns from which TP53 mutation types, including the wild type of the gene, cannot be clearly deduced. We analyzed a total of 236 cases of ovarian HGSCa and tumors of other histology by matching the results of p53 IHC staining and targeted next-generation sequencing (TruSight Tumor 170 panel). Ambiguous IHCs that do not belong to the conventional “all or none” groups were reviewed to distinguish the true wild type (WT) from potentially pathogenic subclonal or mosaic patterns. There were about 9% of sequencing-IHC mismatching cases, which were enriched by the p53 c-terminal encoding nuclear localization signal and oligomerization domain, in which the subcellular locations of p53 protein were affected. Indeed, mutations in the oligomerization domain of the p53 protein frequently revealed an unmatched signal or cytosolic staining (L289Ffs*57 (Ins), and R342*). We conclude that both mutation types and IHC patterns of p53 are important sources of information to provide a precise diagnosis of HGSCa.
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spelling pubmed-89474372022-03-25 p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer Park, Eunhyang Han, Hyunho Choi, Sung-Eun Park, Hyunjin Woo, Ha-Young Jang, Mi Shim, Hyo-Sup Hwang, Sohyun Kang, Haeyoun Cho, Nam-Hoon Diagnostics (Basel) Article High-grade serous carcinoma (HGSCa) of the ovary is featured by TP53 gene mutation. Missense or nonsense mutation types accompany most cases of HGSCa that correlate well with immunohistochemical (IHC) staining results—an all (missense) or none (nonsense) pattern. However, some IHCs produce subclonal or mosaic patterns from which TP53 mutation types, including the wild type of the gene, cannot be clearly deduced. We analyzed a total of 236 cases of ovarian HGSCa and tumors of other histology by matching the results of p53 IHC staining and targeted next-generation sequencing (TruSight Tumor 170 panel). Ambiguous IHCs that do not belong to the conventional “all or none” groups were reviewed to distinguish the true wild type (WT) from potentially pathogenic subclonal or mosaic patterns. There were about 9% of sequencing-IHC mismatching cases, which were enriched by the p53 c-terminal encoding nuclear localization signal and oligomerization domain, in which the subcellular locations of p53 protein were affected. Indeed, mutations in the oligomerization domain of the p53 protein frequently revealed an unmatched signal or cytosolic staining (L289Ffs*57 (Ins), and R342*). We conclude that both mutation types and IHC patterns of p53 are important sources of information to provide a precise diagnosis of HGSCa. MDPI 2022-02-24 /pmc/articles/PMC8947437/ /pubmed/35328131 http://dx.doi.org/10.3390/diagnostics12030579 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
Park, Eunhyang
Han, Hyunho
Choi, Sung-Eun
Park, Hyunjin
Woo, Ha-Young
Jang, Mi
Shim, Hyo-Sup
Hwang, Sohyun
Kang, Haeyoun
Cho, Nam-Hoon
p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title_full p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title_fullStr p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title_full_unstemmed p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title_short p53 Immunohistochemistry and Mutation Types Mismatching in High-Grade Serous Ovarian Cancer
title_sort p53 immunohistochemistry and mutation types mismatching in high-grade serous ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947437/
https://www.ncbi.nlm.nih.gov/pubmed/35328131
http://dx.doi.org/10.3390/diagnostics12030579
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