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The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia.

ABSTRACT: Gastric intraepithelial foveolar type neoplasia (IEFN) is not well defined. In addition, atrophic mucosa (AM) is an important issue to consider when evaluating gastric tumorigenesis. Here, we assessed the clinicopathological characteristics and molecular alterations contributing to the development of IEFN compared with intestinal type neoplasia. We examined the clinicopathological and molecular features of 42 cases of IEFN with low-grade dysplasia (LGD) and those of 77 cases of intraepithelial intestinal type neoplasia (IEIN) with LGD. The clinicopathological and molecular features examined included the AM status, mucin phenotype expression, CDX2 expression, p53 overexpression, ?-catenin intranuclear accumulation, microsatellite instability (MSI), DNA methylation status (low methylation epigenotype [LME], intermediate ME, or high ME), allelic imbalances (AIs), and APC promoter 1B mutations. There were no differences in the frequencies of AM and rates of CDX2 expression between IEFN and IEIN cases. Although no differences in the frequencies of p53 overexpression and MSI were observed between the two histological types, intranuclear expression of ?-catenin was significantly higher in IEIN than in IEFN. In addition, although the rate of LME was significantly higher in IEFN cases than in IEIN cases, IEFN was characterized by AIs at multiple foci. Finally, mutation of the APC promoter 1B, which is a characteristic of gastric adenocarcinoma and proximal polyposis of the stomach (potentially resembling IEFN), was detected in only one IEFN case. These findings suggested that IEFN may be an independent entity in terms of molecular alterations including the presence of multiple AIs and LME.

SUBMITTER: Sugai T

PROVIDER: S-EPMC7683467 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia.

Sugai Tamotsu T Uesugi Noriyuki N Habano Wataru W Sugimoto Ryo R Eizuka Makoto M Fujita Yasuko Y Osakabe Mitsumasa M Toya Yosuke Y Suzuki Hiromu H Matsumoto Takayuki T

Virchows Archiv : an international journal of pathology 20200612 6

Gastric intraepithelial foveolar type neoplasia (IEFN) is not well defined. In addition, atrophic mucosa (AM) is an important issue to consider when evaluating gastric tumorigenesis. Here, we assessed the clinicopathological characteristics and molecular alterations contributing to the development of IEFN compared with intestinal type neoplasia. We examined the clinicopathological and molecular features of 42 cases of IEFN with low-grade dysplasia (LGD) and those of 77 cases of intraepithelial i ...[more]

PMID: 32533343

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Project description:Most gastric cancers develop in patients with chronic gastritis. Chronic gastritis can be classified into two major subtypes: Helicobacter pylori (H. pylori)-induced gastritis and autoimmune gastritis (AIG). Whereas H. pylori-related gastric cancers are more common and have been extensively investigated, the clinicopathological features of gastric cancer with autoimmune gastritis are unclear. Patients diagnosed with gastric cancer and hospitalized in the University Tokyo Hospital from 1998 to 2017 were enrolled. Diagnosis of autoimmune gastritis was based on positivity for serum anti-parietal cell antibody (APCA). We evaluated mucin expression and immune cell infiltration by immunohistochemical staining for MUC5AC, MUC6, PD-L1, CD3, CD11, Foxp3, and PD1. We also examined the presence of bacterial taxa that are reportedly enriched in AIG. Survival analyses of recurrence and 5-year mortality were also performed. In total, 261 patients (76 APCA-positive and 185 APCA-negative) were analyzed. Immunohistochemical staining in the matched cohort showed that AIG-related gastric cancer had higher MUC5AC expression (p = 0.0007) and MUC6 expression (p = 0.0007). Greater infiltration of CD3-positive (p = 0.001), Foxp3-positive (p < 0.001), and PD1-positive cells (p = 0.001); lesser infiltration of CD11b-positive (p = 0.005) cells; and a higher prevalence of Bacillus cereus (p = 0.006) were found in AIG-related gastric cancer patients. The cumulative incidences of gastric cancer recurrence were 2.99% at 2 years, 15.68% at 6 years, and 18.81% at 10 years in APCA-positive patients; they were 12.79% at 2 years, 21.35% at 6 years, and 31.85% at 10 years in APCA-negative patients. The cumulative incidences of mortality were 0% at 3 years and 0% at 5 years in APCA-positive patients; they were 1.52% at 3 years and 2.56% at 5 years in APCA-negative patients. We identified molecular differences between AIG and non-AIG gastric cancer. Differences in T-cell populations and the gastric microbiota may contribute to the pathogenesis of gastric cancers and potentially affect the response to immunotherapy.

Dataset Information

The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia.

Publications

The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia.

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