BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer

Gastric hyperplastic polyps (GHP) are frequently found to be benign polyps and have been considered to have a low carcinogenic potential. The characteristics of the hyperplastic polyp-associated gastric cancer (HPAGC) remain unclear. Therefore, we analyzed samples from 102 GHP patients and identifie...

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Autores principales: Fujiwara-Tani, Rina, Okamoto, Ayaka, Katsuragawa, Hiroyuki, Ohmori, Hitoshi, Fujii, Kiyomu, Mori, Shiori, Kishi, Shingo, Sasaki, Takamitsu, Nakashima, Chie, Kawahara, Isao, Hojo, Yudai, Nishiguchi, Yukiko, Mori, Takuya, Mizumoto, Takeshi, Nagai, Kenta, Luo, Yi, Kuniyasu, Hiroki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657452/
https://www.ncbi.nlm.nih.gov/pubmed/34884530
http://dx.doi.org/10.3390/ijms222312724
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author Fujiwara-Tani, Rina
Okamoto, Ayaka
Katsuragawa, Hiroyuki
Ohmori, Hitoshi
Fujii, Kiyomu
Mori, Shiori
Kishi, Shingo
Sasaki, Takamitsu
Nakashima, Chie
Kawahara, Isao
Hojo, Yudai
Nishiguchi, Yukiko
Mori, Takuya
Mizumoto, Takeshi
Nagai, Kenta
Luo, Yi
Kuniyasu, Hiroki
author_facet Fujiwara-Tani, Rina
Okamoto, Ayaka
Katsuragawa, Hiroyuki
Ohmori, Hitoshi
Fujii, Kiyomu
Mori, Shiori
Kishi, Shingo
Sasaki, Takamitsu
Nakashima, Chie
Kawahara, Isao
Hojo, Yudai
Nishiguchi, Yukiko
Mori, Takuya
Mizumoto, Takeshi
Nagai, Kenta
Luo, Yi
Kuniyasu, Hiroki
author_sort Fujiwara-Tani, Rina
collection PubMed
description Gastric hyperplastic polyps (GHP) are frequently found to be benign polyps and have been considered to have a low carcinogenic potential. The characteristics of the hyperplastic polyp-associated gastric cancer (HPAGC) remain unclear. Therefore, we analyzed samples from 102 GHP patients and identified 20 low-grade atypical GHPs (19.6%), 7 high-grade atypical GHPs (6.9%), and 5 intramucosal cancer samples (4.9%). GHP atypia was more common in the elderly and increased with increasing polyp size. In particular, polyps larger than 1 cm were associated with a higher grade and cancer. Furthermore, mucus production decreased with increasing atypia. Although no correlation was found between atypia and Helicobacter pylori infection or intestinal metaplasia, enhanced proliferative ability (Ki-67) did correlate with atypia, as did nuclear 8-hydroxy-2’-deoxyguanosine levels. Interestingly, 4-hydroxynonenal levels in granulation tissue and the area ratio of granulation tissue within polyps also correlated with GHP atypia. In five cases of HPAGC, three cases exhibited caudal type homeobox transcription factor (CDX2)-positive cells and a mixed mucin phenotype, which is considered to be related to H. pylori infection. By contrast, two cases were CDX2 negative, with a gastric mucin phenotype, and H. pylori infection was not observed in the tumor or the surrounding mucosa. In these cases, a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (V600E) was detected. All cancer samples showed high stemness and p53 protein accumulation, but no KRAS mutations. The molecular and phenotypic characteristics of the cases characterized by BRAF mutations may represent a novel subtype of HPAGC, reflecting a conserved pathway to oncogenesis that does not involve H. pylori infection. These findings are worthy of further investigation in a large-scale study with a substantial cohort of HPAGC patients to establish their clinical significance.
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spelling pubmed-86574522021-12-10 BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer Fujiwara-Tani, Rina Okamoto, Ayaka Katsuragawa, Hiroyuki Ohmori, Hitoshi Fujii, Kiyomu Mori, Shiori Kishi, Shingo Sasaki, Takamitsu Nakashima, Chie Kawahara, Isao Hojo, Yudai Nishiguchi, Yukiko Mori, Takuya Mizumoto, Takeshi Nagai, Kenta Luo, Yi Kuniyasu, Hiroki Int J Mol Sci Article Gastric hyperplastic polyps (GHP) are frequently found to be benign polyps and have been considered to have a low carcinogenic potential. The characteristics of the hyperplastic polyp-associated gastric cancer (HPAGC) remain unclear. Therefore, we analyzed samples from 102 GHP patients and identified 20 low-grade atypical GHPs (19.6%), 7 high-grade atypical GHPs (6.9%), and 5 intramucosal cancer samples (4.9%). GHP atypia was more common in the elderly and increased with increasing polyp size. In particular, polyps larger than 1 cm were associated with a higher grade and cancer. Furthermore, mucus production decreased with increasing atypia. Although no correlation was found between atypia and Helicobacter pylori infection or intestinal metaplasia, enhanced proliferative ability (Ki-67) did correlate with atypia, as did nuclear 8-hydroxy-2’-deoxyguanosine levels. Interestingly, 4-hydroxynonenal levels in granulation tissue and the area ratio of granulation tissue within polyps also correlated with GHP atypia. In five cases of HPAGC, three cases exhibited caudal type homeobox transcription factor (CDX2)-positive cells and a mixed mucin phenotype, which is considered to be related to H. pylori infection. By contrast, two cases were CDX2 negative, with a gastric mucin phenotype, and H. pylori infection was not observed in the tumor or the surrounding mucosa. In these cases, a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (V600E) was detected. All cancer samples showed high stemness and p53 protein accumulation, but no KRAS mutations. The molecular and phenotypic characteristics of the cases characterized by BRAF mutations may represent a novel subtype of HPAGC, reflecting a conserved pathway to oncogenesis that does not involve H. pylori infection. These findings are worthy of further investigation in a large-scale study with a substantial cohort of HPAGC patients to establish their clinical significance. MDPI 2021-11-25 /pmc/articles/PMC8657452/ /pubmed/34884530 http://dx.doi.org/10.3390/ijms222312724 Text en © 2021 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
Fujiwara-Tani, Rina
Okamoto, Ayaka
Katsuragawa, Hiroyuki
Ohmori, Hitoshi
Fujii, Kiyomu
Mori, Shiori
Kishi, Shingo
Sasaki, Takamitsu
Nakashima, Chie
Kawahara, Isao
Hojo, Yudai
Nishiguchi, Yukiko
Mori, Takuya
Mizumoto, Takeshi
Nagai, Kenta
Luo, Yi
Kuniyasu, Hiroki
BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title_full BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title_fullStr BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title_full_unstemmed BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title_short BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
title_sort braf mutation is associated with hyperplastic polyp-associated gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657452/
https://www.ncbi.nlm.nih.gov/pubmed/34884530
http://dx.doi.org/10.3390/ijms222312724
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