# A gastric invasive tubular adenocarcinomatous lesion arising from foveolar-type neoplasia: molecular histogenesis

## TL;DR

This paper describes a rare gastric tumor with two components and suggests that one may have developed from the other based on molecular and histological findings.

## Contribution

The study provides new insights into the molecular histogenesis of gastric adenocarcinoma from foveolar-type neoplasia.

## Key findings

- TDA surrounded IFN histologically, suggesting a potential developmental origin.
- Allelic imbalances at 3p and TP53 were found only in the TDA component.
- The tumor was microsatellite stable with low DNA methylation in both components.

## Abstract

Here, we report a rare case of a depressed lesion exhibiting both tubular differentiated adenocarcinomatous (TDA) and intraepithelial foveolar neoplasia (IFN) components (with the histological appearance of foveolar hyperplasia due to low-grade atypia). Histologically, the TDA surrounded the IFN, suggesting that the TDA may have originated from the IFN. Therefore, we examined molecular alterations in the TDA and IFN components separately. MUC5AC and MUC6 expression was observed immunohistochemically in both components. p53 expression was wild type in both components, suggesting no mutation of TP53. We investigated allelic imbalances at multiple loci (1p, 3p, 4p, 5q, 8q, 9p, 13q, TP53, 18q, and 22q), mutations (KRAS, BRAF, and GNAS), and DNA methylation and microsatellite status in both components using PCR-based analyses. Although multiple allelic imbalances were common to both components, allelic imbalances at 3p and TP53 were found only in the TDA component. No mutations were found, and DNA methylation status was low epigenotype for both components. Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA.