Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry

Abstract Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was...

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Autores principales:	Masahiro Watanabe, Takeshi Kuwata, Ayumi Setsuda, Masanori Tokunaga, Akio Kaito, Shizuki Sugita, Akiko Tonouchi, Takahiro Kinoshita, Masato Nagino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d806586381e2448aad2937df71280e3f
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spelling	oai:doaj.org-article:d806586381e2448aad2937df71280e3f2021-12-02T10:54:30ZMolecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry10.1038/s41598-021-83711-12045-2322https://doaj.org/article/d806586381e2448aad2937df71280e3f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83711-1https://doaj.org/toc/2045-2322Abstract Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was analysed by immunohistochemistry and in situ hybridisation. Programmed death ligand 1 (PD-L1) was expressed in 98.9% of tumour-infiltrating immune cells (TIICs) and 6.7% of tumour cells (TCs). Epstein–Barr virus (EBV) was detected in 18 patients (20.2%). Overexpression of human epidermal growth factor receptor 2 and deficiency of mismatch repair (MMR) protein expression were observed in 5.6% and 1.1% of cases, respectively. Moreover, we used next-generation sequencing to determine the gene mutation profiles of a subset of the 50 most recent patients. The most frequently mutated genes were TP53 (42.0%) followed by SMAD4 (18.0%) and PTEN (16.0%), all of which are tumour suppressor genes. A high frequency of PD-L1 expression in TIICs and a high EBV infection rate suggest immune checkpoint inhibitors for treatment of GSC despite a relatively low frequency of deficient MMR gene expression. Other molecular characteristics such as PTEN and SMAD4 mutations might be considered to develop new treatment strategies.Masahiro WatanabeTakeshi KuwataAyumi SetsudaMasanori TokunagaAkio KaitoShizuki SugitaAkiko TonouchiTakahiro KinoshitaMasato NaginoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masahiro Watanabe Takeshi Kuwata Ayumi Setsuda Masanori Tokunaga Akio Kaito Shizuki Sugita Akiko Tonouchi Takahiro Kinoshita Masato Nagino Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
description	Abstract Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was analysed by immunohistochemistry and in situ hybridisation. Programmed death ligand 1 (PD-L1) was expressed in 98.9% of tumour-infiltrating immune cells (TIICs) and 6.7% of tumour cells (TCs). Epstein–Barr virus (EBV) was detected in 18 patients (20.2%). Overexpression of human epidermal growth factor receptor 2 and deficiency of mismatch repair (MMR) protein expression were observed in 5.6% and 1.1% of cases, respectively. Moreover, we used next-generation sequencing to determine the gene mutation profiles of a subset of the 50 most recent patients. The most frequently mutated genes were TP53 (42.0%) followed by SMAD4 (18.0%) and PTEN (16.0%), all of which are tumour suppressor genes. A high frequency of PD-L1 expression in TIICs and a high EBV infection rate suggest immune checkpoint inhibitors for treatment of GSC despite a relatively low frequency of deficient MMR gene expression. Other molecular characteristics such as PTEN and SMAD4 mutations might be considered to develop new treatment strategies.
format	article
author	Masahiro Watanabe Takeshi Kuwata Ayumi Setsuda Masanori Tokunaga Akio Kaito Shizuki Sugita Akiko Tonouchi Takahiro Kinoshita Masato Nagino
author_facet	Masahiro Watanabe Takeshi Kuwata Ayumi Setsuda Masanori Tokunaga Akio Kaito Shizuki Sugita Akiko Tonouchi Takahiro Kinoshita Masato Nagino
author_sort	Masahiro Watanabe
title	Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
title_short	Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
title_full	Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
title_fullStr	Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
title_full_unstemmed	Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
title_sort	molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d806586381e2448aad2937df71280e3f
work_keys_str_mv	AT masahirowatanabe molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT takeshikuwata molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT ayumisetsuda molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT masanoritokunaga molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT akiokaito molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT shizukisugita molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT akikotonouchi molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT takahirokinoshita molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry AT masatonagino molecularandpathologicalanalysesofgastricstumpcancerbynextgenerationsequencingandimmunohistochemistry
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Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry

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