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Abstract

Recent studies have described a spasmolytic polypeptide-expressing metaplastic cell lineage (SPEM) in the gastric fundic mucosa associated with both chronic H. pylori infection and gastric adenocarcinoma. We investigated the association of SPEM both with early gastric adenocarcinoma and in biopsies taken from patients prior to diagnosis of cancer. Two cohorts were examined. First, gastric resections from 29 patients with early gastric cancer were examined. Second, biopsies taken from 18 patients prior to the diagnosis of gastric cancer were compared with their respective resection specimens as well as with control biopsies from a cohort of 19 patients diagnosed with gastritis without subsequent development of cancer. The presence of SPEM and intestinal metaplasia (IM) adjacent to and distant from the cancer was compared and spasmolytic polypeptide (SP) immunostaining within dysplastic/cancerous cells was identified. SPEM was present adjacent to cancer in all early cancer cases where the tumor was located in the body or at the body/antrum junction, and was present in the body mucosa distant from the cancer in 76% of cases. Intestinal metaplasia was found adjacent to the tumor in 76% of cases and in body sections in 52% of resections. SP immunostaining was noted within cancer cells in 62% of tumors, and within dysplastic cells in 76% of resections where dysplasia was present. SPEM was present in 82% of the biopsies obtained prior to the diagnosis of cancer, compared with only 37% in the gastritis cohort. IM was present in only 57% of biopsies. In conclusion, SPEM is strongly associated with early gastric cancers and is observed in gastric biopsies prior to the development of cancer. In addition, early gastric cancers demonstrated a high incidence of SP expression. These results suggest that SPEM merits consideration as an important pre-neoplastic gastric lesion.

Pyloric metaplasia, pseudopyloric metaplasia, ulcer‐associated cell lineage and spasmolytic polypeptide‐expressing metaplasia: reparative lineages in the gastrointestinal mucosa

“…The observation of SPEM emerging rapidly after acute parietal cell loss induced by DMP777, L635 or high dose tamoxifen is consistent with this lineage performing a role in the response to injury [41–43]. SPEM appears to resolve following resolution of injury and can often appear as a highly localized phenomenon [29,41,43]. Thus, acute ulceration injury in the stomach is associated with the appearance of SPEM around ulcers and SPEM contributes to the healing of these lesions [32,39,44].…”

“…Spasmolytic polypeptide-expressing metaplasia (SPEM) was identified more than goblet cell-containing intestinal metaplasia in an initial cohort from the United States [28] and in association with early gastric cancers in Iceland [29]. This lineage showed many of the characteristics of deep antral gland cells or Brunner’s gland cells.…”

Oxyntic Atrophy, Metaplasia, and Gastric Cancer

“…Recent studies have suggested that both SPEM and intestinal metaplasia may be pre-neoplastic metaplasias. In three separate studies, SPEM was associated with 90% of resected gastric cancers (23, 25, 29). TFF2 was also expressed in greater than 50% of early gastric cancers from Iceland (30).…”

“…In humans, two types of metaplasia arise in the milieue of oxyntic atrophy and inflammation: intestinal metaplasia and spasmolytic polypeptide expressing metaplasia (SPEM). Both intestinal metaplasia and SPEM have been associated with the progression to intestinal type gastric cancer (8, 17–25). Thus, oxyntic atrophy in association with prominent inflammation incites the induction of gastric lineages that predispose to the development of gastric cancer.…”

Gastric Metaplasia Induced by Helicobacter pylori Is Associated with Enhanced SOX9 Expression via Interleukin-1 Signaling

“…Parietal cell atrophy causes increased proliferation of normal stem/progenitor cells in the isthmus (21). Clinically, the distributions of chronic parietal cell atrophy and SPEM have been associated with gastric cancer in 90% of resected stomachs (22,23), suggesting that SPEM could represent a surrogate marker of gastric cancer risk. However, the molecular mechanisms leading to SPEM and the expansion of progenitors in H. pylori-induced gastritis are largely unknown.…”