Superficially elevated-type serrated hyperplastic lesion of the stomach with minute adenocarcinoma.

We report a case of gastric serrated hyperplastic lesion with minute adenocarcinoma. A 65-year-old Japanese man underwent endoscopic submucosal dissection to the superficially elevated-type (0-IIa) lesion located at the lesser curvature of the gastric angle. Histological observation revealed hyperplastic change of foveolar epithelium with serrated glandular structure as well as a minute tubular adenocarcinoma component. Immunohistochemically, the lesion demonstrated gastrointestinal, predominantly gastric, phenotype (MUC5AC++, MUC6+, MUC2+, CD10-). Positive p53 immunoreactivity was detected in the carcinoma component of the lesion with a point mutation (G877T; R209I) of the gene and microsatellite instability of the BAT-RII locus; however, immunoreactivity of the mismatch repair gene product hMLH1 was well preserved in the cancer as well as in the hyperplastic lesion. The hyperplastic lesion with serrated glandular pattern would be a precancerous lesion of adenocarcinoma of the stomach.

Prognostic significance of intestinal claudins in high-risk synchronous and metachronous multiple gastric epithelial neoplasias after initial endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is useful in en bloc curative resection and enables patients with early gastric carcinoma (GC) to have a better quality of life. But metachronous recurrence of GC at other sites in the stomach has become a major issue after initial ESD. The purpose of the present paper was to examine gastric (claudin-18) and intestinal claudin (claudin-3 and claudin-4) expression in early GC on immunohistochemistry to clarify the association with clinicopathology, mucin phenotypes, microsatellite instability (MSI) status and the incidence of synchronous and metachronous gastric epithelial neoplasias after initial ESD. According to intestinal claudin expression, a total of 73 early GC were divided into two groups: intestinal claudin-positive (I-CLDN(+)) phenotype (n = 52; 71%); and intestinal claudin-negative (I-CLDN(-)) phenotype (n = 21; 29%). Although no significant association was found with clinicopathology and the MSI status, the I-CLDN(+) early GC correlated with the mucin phenotypes and had a significantly higher incidence of synchronous and metachronous multiple GC and gastric adenomas (P = 0.049). These results indicate that early GC demonstrating I-CLDN(+) phenotype have a high risk of synchronous and metachronous secondary gastric epithelial neoplasias.

Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer.

BACKGROUND AND AIMS: Many investigators have reported flat and depressed lesions as a new type of precursor of colorectal cancer. In our previous study, we determined that mutations in the BRAF gene may contribute to colorectal carcinogenesis by inhibiting apoptosis. However, the relationship among BRAF mutations, morphology and apoptosis in early colorectal cancer has not been clear. Therefore, gene alternation, morphology, and apoptosis in early colorectal cancer were investigated. MATERIALS AND METHODS: Forty-five flat and depressed early colorectal cancer samples and 43 polypoid early colorectal cancer samples were analyzed. Mutations in the BRAF gene and the K-ras gene were examined by direct sequence analysis, and proliferative activity and induction of apoptosis were evaluated using immunohistochemical examination. RESULTS FINDINGS: BRAF mutations were found in 5 (11.1%) of 45 flat and depressed early colorectal cancer samples. No BRAF alteration was found in polypoid early colorectal cancer samples. Mutations in the K-ras gene were detected in 13 (30.2%) of 43 polypoid early colorectal cancer samples. The rate of submucosal invasion of the samples with BRAF mutations was significantly higher than that of the samples with K-ras mutations (p<0.05). INTERPRETATION/CONCLUSIONS: BRAF and K-ras mutations were independent factors that influenced morphology in early colorectal cancer. In this study, the relationship between BRAF mutation and apoptosis is not so clear, but BRAF mutations and inhibition in apoptosis may play an important role in the developmental process of flat and depressed early colorectal cancer.

Gastric and intestinal claudin expression at the invasive front of gastric carcinoma.

Like gastric and intestinal mucins, the tight junction proteins called claudins can be used to determine the differentiation of gastric mucosa. We investigated the expression of claudins in gastric cancer and proposed a new claudin-based gastric cancer classification system. The expression of gastric (claudin-18) and intestinal (claudin-3 and claudin-4) claudins in non-neoplastic gastric mucosa (with intestinal metatplasia [IM], 78 cases; without IM, 88 cases) and 94 gastric cancers was analyzed immunohistochemically, as was the expression of gastric (MUC5A and MUC6) and intestinal (CD10 and MUC2) mucins. Heterogeneous expression of claudin-3, claudin-4 and claudin-18 was detected in advanced gastric cancer; however, there was no significant association between the claudins and the clinicopathological parameters. These gastric cancer tissues were also subclassified into claudin-based phenotypes: gastric claudin (G-CLDN), 28 cases (30%); intestinal claudin (I-CLDN), 41 cases (44%); and unclassified claudin (U-CLDN), 25 cases (26%). Interestingly, the U-CLDN gastric cancers had worse malignancy grades, not only in size and invasiveness but also in potential metastatic ability and patient outcome. Although the mucin-based gastric cancer classification was also assessed, no significant correlation was found between mucin production and clinicopathological parameters. These observations suggest that loss of claudin expression may enhance the grade of malignancy of gastric cancer in vivo. Classification of gastric cancers using gastric and intestinal claudins is a good biomarker for assessing the risk of poor prognosis.