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BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer

Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan
Miyoshi Central Hospital, 10531 Higashi-Sakaya-cho, Miyoshi 728-8502, Japan
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
Authors to whom correspondence should be addressed.
Academic Editor: Peter J.K. Kuppen
Int. J. Mol. Sci. 2021, 22(23), 12724;
Received: 29 October 2021 / Revised: 21 November 2021 / Accepted: 22 November 2021 / Published: 25 November 2021
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. View Full-Text
Keywords: gastric hyperplastic polyp; gastric cancer; BRAF mutation; H. pylori; oxidative stress gastric hyperplastic polyp; gastric cancer; BRAF mutation; H. pylori; oxidative stress
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MDPI and ACS Style

Fujiwara-Tani, R.; Okamoto, A.; Katsuragawa, H.; Ohmori, H.; Fujii, K.; Mori, S.; Kishi, S.; Sasaki, T.; Nakashima, C.; Kawahara, I.; Hojo, Y.; Nishiguchi, Y.; Mori, T.; Mizumoto, T.; Nagai, K.; Luo, Y.; Kuniyasu, H. BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer. Int. J. Mol. Sci. 2021, 22, 12724.

AMA Style

Fujiwara-Tani R, Okamoto A, Katsuragawa H, Ohmori H, Fujii K, Mori S, Kishi S, Sasaki T, Nakashima C, Kawahara I, Hojo Y, Nishiguchi Y, Mori T, Mizumoto T, Nagai K, Luo Y, Kuniyasu H. BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer. International Journal of Molecular Sciences. 2021; 22(23):12724.

Chicago/Turabian Style

Fujiwara-Tani, Rina, Ayaka Okamoto, Hiroyuki Katsuragawa, Hitoshi Ohmori, Kiyomu Fujii, Shiori Mori, Shingo Kishi, Takamitsu Sasaki, Chie Nakashima, Isao Kawahara, Yudai Hojo, Yukiko Nishiguchi, Takuya Mori, Takeshi Mizumoto, Kenta Nagai, Yi Luo, and Hiroki Kuniyasu. 2021. "BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer" International Journal of Molecular Sciences 22, no. 23: 12724.

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