Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784761252584620032 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9344582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wiley Publishing Asia Pty Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yamashiroyuya molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT yanaiyuka molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT takedatsutomu molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT hayashitakuo molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT akazawayoichi molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT yatagainoboru molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT ueyamahiroya molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT eguchihidetaka molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT nagaharaakihito molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT yaotakashi molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis AT saitotsuyoshi molecularandclinicopathologicalanalysisofthreecasesofgastricjuvenilepolyposis |