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.
Int J Mol Sci. 2021 Nov 25;22(23):12724. doi: 10.3390/ijms222312724.
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 infection. By contrast, two cases were CDX2 negative, with a gastric mucin phenotype, and 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 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.
胃增生性息肉（Gastric hyperplastic polyps，GHP）通常被认为是良性息肉，其癌变潜能较低。然而，增生性息肉相关胃癌（hyperplastic polyp-associated gastric cancer，HPAGC）的特征仍不清楚。因此，我们分析了 102 例 GHP 患者的样本，发现 20 例低级别不典型 GHPs（19.6%）、7 例高级别不典型 GHPs（6.9%）和 5 例黏膜内癌样本（4.9%）。GHP 不典型性在老年人中更为常见，且随息肉增大而增加。特别是，直径大于 1cm 的息肉与高级别和癌症相关。此外，随着不典型性的增加，黏液产生减少。虽然不典型性与幽门螺杆菌感染或肠上皮化生之间没有相关性，但Ki-67 增殖能力和核 8-羟基-2'-脱氧鸟苷水平与不典型性相关。有趣的是，肉芽组织中的 4-羟基壬烯醛水平和息肉内肉芽组织的面积比也与 GHP 不典型性相关。在 5 例 HPAGC 中，有 3 例表现为尾型同源盒转录因子（caudal type homeobox transcription factor，CDX2）阳性细胞和混合黏液表型，这被认为与感染有关。相比之下，有 2 例为 CDX2 阴性，表现为胃黏液表型，肿瘤或周围黏膜均未观察到感染。在这些病例中，检测到 v-raf 鼠肉瘤病毒癌基因同源物 B1（v-raf murine sarcoma viral oncogene homolog B1，BRAF）突变（V600E）。所有的癌症样本均表现出高干性和 p53 蛋白积累，但无 KRAS 突变。具有 BRAF 突变的病例的分子和表型特征可能代表一种新型的 HPAGC 亚型，反映了一种不涉及感染的保守致癌途径。这些发现值得在大规模研究中进一步探讨，该研究需要有大量的 HPAGC 患者队列来确定其临床意义。
