The biological significance and histogenesis of PACM in the gastric mucosa, which was first described in 1993 [1], remain uncertain [2]. Previous studies examining PACM in the stomach have been limited to small numbers of cases. Therefore, the present study with a large cohort might more closely reflect the true frequency of PACM in the stomach. This is the first study to examine the frequency, location, and clinicopathological features of PACM in the context of H. pylori infection.
In the current study, PACM was present in patients with previous or current H. pylori infection but not in those without H. pylori infection, suggesting that H. pylori might play a crucial role in the development of PACM. Doglioni et al. reported that 75% of patients with PACM exhibited H. pylori-like organisms in the stomach only by histological examination [1], although the authors did not confirm the presence of H. pylori infection using other diagnostic methods. Therefore, the present study was the first to clarify the close association between H. pylori infection and PACM. In addition, there was no significant difference in the rate of PACM between the patients with past and current H. pylori infection. Therefore, it remains clear whether H. pylori eradication might impact the development of PACM.
In the current cohort, most areas of PACM were in the antrum, in agreement with a previous study reporting that PACM was more frequent in the antrum (0.8%) than in the corpus (0.16%) [1]. In H. pylori gastritis, gastric inflammation and atrophy tend to be observed in the antrum rather than in the corpus [6], which might partially explain the higher frequency of PACM in the antrum than in the corpus among the patients with CHI. In addition, inflammation and atrophy scores were reported to be higher in the antrum even after a long eradication period in patients with H. pylori infection than in those without H. pylori infection [6]. PACM has been reported to occur near the glandular stomach–jejunal anastomosis in a rat model of duodenal content reflux, suggesting that gastric inflammation, atrophy, and bile acids might play an important role in the development of PACM in the antrum [5].
Two types of differentiation patterns are considered to underlie the pathogenesis of PACM: differentiation from the parietal cell lineage and differentiation from stem cells [4, 12]. Gastric stem cells are found in the proliferative zone of the neck [13], and the expression of Ki-67 observed in the neck in the present study provides support for the latter possibility. In addition, the overlap between Bcl-10 and MUC6 expression near the gastric neck by double immunofluorescence staining lends further support that PACM might be arising from this location. Furthermore, PACM was frequently accompanied by pyloric-type glands, as previously reported [1], implicating a relationship between PACM and pyloric-type glands.
Among the metaplastic lesions found in the stomach, intestinal metaplasia is recognized as pre- and/or paracancerous atrophic lesions preceding gastric cancer [14]. Pyloric/pseudopyloric metaplasia has been reported in patients with CHI and advanced inflammation and atrophy [7]. In the present study, the inflammation scores in A2 were significantly lower in the PACM group than in the non-PACM group among those with CHI and the atrophy scores tended to be lower in the PACM group than in the non-PACM group among those with CHI. Additionally, the atrophy scores were significantly lower in the PACM group than in the non-PACM group. Krishnamurthy et al. reported that PACM was found in normal or minimally inflamed gastric mucosa in pediatric gastric mucosa [4], suggesting that PACM might appear in mild inflammatory and atrophic conditions of the gastric mucosa. Severe inflammation and atrophy might alleviate PACM or might the emergence of other types of metaplasia from PACM. PACM was found in normal or minimally inflamed gastric mucosa [4].
In the presence of H. pylori gastritis, the risk of gastric cancer has been reported to increase with the progression of atrophy [15, 16]. The current study findings do not clarify whether PACM might be associated with gastric cancer. Although the association between H. pylori and PACM is strongly suggested, the frequency of PACM is much lower than that of gastric cancer and future studies with larger cohorts of PACM are warranted to examine its association with gastric cancer.
Omeprazole was reported to cause PACM after six months of treatment in rats [17]. In humans, PACM is often observed in patients with autoimmune gastritis [3]. Hypergastrinemia is a shared feature between the oral administration of proton pump inhibitors and autoimmune gastritis; however, we did not find a relationship between hypergastrinemia and PACM in patients with H. pylori gastritis in the present study.
There are several limitations in the present study. First, this was a retrospective single-center study. Second, we examined biopsy specimens, which might not reflect the status of the entire gastric mucosa because PACM exhibits a patchy distribution pattern.
In conclusion, in the present study, we found that the development of PACM, especially in the antrum, was closely association with H. pylori infection. In addition, we found that PACM in the gastric mucosa was associated with pyloric metaplasia. Whether these changes in gastric mucosa influence due to H. pylori infection are associated with gastric cancer remains unclear, and future studies are necessary to elucidate the association of PACM with the development of gastric cancer.