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Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis

BACKGROUND AND AIM: Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9–50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to el...

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Autores principales: Yamashiro, Yuya, Yanai, Yuka, Takeda, Tsutomu, Hayashi, Takuo, Akazawa, Yoichi, Yatagai, Noboru, Ueyama, Hiroya, Eguchi, Hidetaka, Nagahara, Akihito, Yao, Takashi, Saito, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Publishing Asia Pty Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344582/
https://www.ncbi.nlm.nih.gov/pubmed/35928693
http://dx.doi.org/10.1002/jgh3.12781
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author Yamashiro, Yuya
Yanai, Yuka
Takeda, Tsutomu
Hayashi, Takuo
Akazawa, Yoichi
Yatagai, Noboru
Ueyama, Hiroya
Eguchi, Hidetaka
Nagahara, Akihito
Yao, Takashi
Saito, Tsuyoshi
author_facet Yamashiro, Yuya
Yanai, Yuka
Takeda, Tsutomu
Hayashi, Takuo
Akazawa, Yoichi
Yatagai, Noboru
Ueyama, Hiroya
Eguchi, Hidetaka
Nagahara, Akihito
Yao, Takashi
Saito, Tsuyoshi
author_sort Yamashiro, Yuya
collection PubMed
description BACKGROUND AND AIM: Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9–50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to elucidate the mechanisms of malignant transformation underlying this condition in three cases of gastric JP. METHODS: We selected polyps from each patient displaying varying degrees of atypia and their nearby normal polyps and compared them using immunohistochemistry, Sanger sequencing, and loss of heterozygosity (LOH) analysis of SMAD4, BMPR1A, and TP53. RESULTS: Two of the three cases were suspected of having germline SMAD4 mutations based on their familial medical histories; the remaining case was found to have a SMAD4 germline mutation following preoperative genetic testing. All three cases were shown to present with both SMAD4 positive and negative areas across each lesion, with the neoplastic lesions tending to show stronger nuclear SMAD4 expression. This expression was closely associated with the SMAD4 LOH status; however, we also noted paradoxical SMAD4 expression in the neoplastic lesions despite the biallelic inactivation of SMAD4 revealed in the genetic evaluation. CONCLUSIONS: These data suggest that strong nuclear expression of SMAD4, even when seemingly paradoxical, seems to be closely associated with dysplastic polyps in JP. Complete inactivation of SMAD4 was not shown to be essential for the development of dysplastic polyps in gastric JP, and other pathways seemed to be involved in the acquisition of the malignant phenotype.
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spelling pubmed-93445822022-08-03 Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis Yamashiro, Yuya Yanai, Yuka Takeda, Tsutomu Hayashi, Takuo Akazawa, Yoichi Yatagai, Noboru Ueyama, Hiroya Eguchi, Hidetaka Nagahara, Akihito Yao, Takashi Saito, Tsuyoshi JGH Open Original Articles BACKGROUND AND AIM: Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9–50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to elucidate the mechanisms of malignant transformation underlying this condition in three cases of gastric JP. METHODS: We selected polyps from each patient displaying varying degrees of atypia and their nearby normal polyps and compared them using immunohistochemistry, Sanger sequencing, and loss of heterozygosity (LOH) analysis of SMAD4, BMPR1A, and TP53. RESULTS: Two of the three cases were suspected of having germline SMAD4 mutations based on their familial medical histories; the remaining case was found to have a SMAD4 germline mutation following preoperative genetic testing. All three cases were shown to present with both SMAD4 positive and negative areas across each lesion, with the neoplastic lesions tending to show stronger nuclear SMAD4 expression. This expression was closely associated with the SMAD4 LOH status; however, we also noted paradoxical SMAD4 expression in the neoplastic lesions despite the biallelic inactivation of SMAD4 revealed in the genetic evaluation. CONCLUSIONS: These data suggest that strong nuclear expression of SMAD4, even when seemingly paradoxical, seems to be closely associated with dysplastic polyps in JP. Complete inactivation of SMAD4 was not shown to be essential for the development of dysplastic polyps in gastric JP, and other pathways seemed to be involved in the acquisition of the malignant phenotype. Wiley Publishing Asia Pty Ltd 2022-06-28 /pmc/articles/PMC9344582/ /pubmed/35928693 http://dx.doi.org/10.1002/jgh3.12781 Text en © 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yamashiro, Yuya
Yanai, Yuka
Takeda, Tsutomu
Hayashi, Takuo
Akazawa, Yoichi
Yatagai, Noboru
Ueyama, Hiroya
Eguchi, Hidetaka
Nagahara, Akihito
Yao, Takashi
Saito, Tsuyoshi
Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title_full Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title_fullStr Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title_full_unstemmed Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title_short Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
title_sort molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344582/
https://www.ncbi.nlm.nih.gov/pubmed/35928693
http://dx.doi.org/10.1002/jgh3.12781
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