A case report of superficially spreading gastric cancer with distinct molecular features: a novel approach for evaluating gastric molecular carcinogenesis

A 62-year-old woman was admitted to our hospital because of epigastralgia. Upper gastrointestinal endoscopy revealed a superficial spreading type of gastric tumor (superficially spreading gastric cancer, SSGC) with a central depression in the lesser curvature of the pyloric antrum. Histologically, the tumor was diagnosed as a differentiated-type adenocarcinoma. The bottom of the depression was in muscularis propria, whereas the surrounding lesion was within mucosa. Neither p53 overexpression nor MLH1 expression was found in either layer of the lesion by immunostaining. However, proliferative activity was higher in the invasive area of the lesion than in the intramucosal area. Expression of gastric mucin was seen in both areas of the lesion. Isolated crypts were analyzed using PCR to assess loss of heterozygosity (LOH) at chromosomal loci, microsatellite instability (MSI), and methylation status in the tumor. In both the intramucosal and invasive areas of the lesion, multiple losses of heterozygosity (LOHs) and increased methylation were observed, while MSI was observed only in the invasive lesion. We hypothesized that multiple LOHs and extensive methylation are closely associated with the early development of a subset of differentiated-type SSGCs, whereas MSI plays an essential role in the progression of SSGC with gastric phenotype.