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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer
Rina Fujiwara-Tani1, Ayaka Okamoto1, Hiroyuki Katsuragawa1
1Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan.
International Journal of Molecular Sciences
|December 10, 2021
Summary
Gastric hyperplastic polyps (GHPs) can develop atypia and cancer, especially in larger polyps. BRAF mutations may indicate a novel subtype of GHP-associated gastric cancer independent of H. pylori.
Area of Science:
- Gastroenterology
- Oncology
- Pathology
Background:
- Gastric hyperplastic polyps (GHPs) are common benign lesions.
- Their carcinogenic potential and associated gastric cancer (HPAGC) characteristics are not well understood.
Purpose of the Study:
- To analyze the atypia and malignant potential of GHPs.
- To investigate the molecular and phenotypic characteristics of HPAGC.
Main Methods:
- Analysis of 102 GHP patient samples.
- Histopathological evaluation for atypia and cancer.
- Immunohistochemistry for proliferation markers (Ki-67), p53, CDX2.
- Molecular analysis for BRAF and KRAS mutations.
- Assessment of Helicobacter pylori infection and intestinal metaplasia.
Main Results:
- Atypia and cancer were identified in 19.6% and 4.9% of GHPs, respectively.
- GHP atypia correlated with older age, larger polyp size (>1 cm), decreased mucus production, increased proliferation (Ki-67), and DNA damage (8-hydroxy-2'-deoxyguanosine).
- HPAGC cases showed distinct phenotypes: H. pylori-associated (CDX2+, mixed mucin) and H. pylori-negative (CDX2-, gastric mucin) with BRAF V600E mutations, high stemness, and p53 accumulation.
Conclusions:
- GHP atypia and malignant transformation are associated with specific clinical and molecular factors.
- BRAF-mutated HPAGC may represent a novel subtype unrelated to H. pylori infection.
- Further large-scale studies are needed to confirm the clinical significance of these findings.
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