Short-chain fatty acids (SCFAs), 2-4 carbon monocarboxylates including acetate, propionate and butyrate, are known to have a variety of physiological and pathophysiological effects on the intestine. Previously, we reported that the SCFA receptor, G-protein coupled receptor 43 (GPR43), is expressed by enteroendocrine and mucosal mast cells in the rat intestine. In the present study, expression and localization of GPR43 were investigated in the human large intestine. Gene and protein expression of GPR43 in the human ascending colon was analyzed by reverse transcriptase/polymerase chain reaction and Western blotting, respectively. In addition, localization of GPR43 was investigated by immunohistochemistry. In RT-PCR analysis, GPR43 mRNA was detected in whole wall mRNA samples. Western blotting analysis revealed the expression of GPR43 protein in whole wall and scraped mucosa protein samples, but not in muscle or submucosa. GPR43 immunoreactivity was observed in the intracellularly in enterocytes and in the peptide YY-immunoreactive enteroendocrine cells. These results indicate that the short chain fatty acid receptor, GPR43 is expressed by enteroendocrine L cells containing peptide YY in the human large intestine.

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Aggressive angiomyxoma (AA) is a rare mesenchymal tumor that preferentially involves the pelvic and perineal regions, and is characterized by frequent local recurrences. We describe here a case of large AA in a 31-year-old woman. The patient was admitted to our hospital with a mass in the perineal region, associated with severe menstrual pain. Although her past medical history was unremarkable, she had spotty pigmentation on the lips. Magnetic resonance imaging showed a large mass in the abdominal pelvis traversing the pelvic diaphragm just to the right of the anus, and the border between the tumor and the rectal wall was indistinct. Pathology examination of a frozen intraoperative specimen suggested AA, and, therefore, we completely resected the tumor, using a combined abdominoperineal approach. The tumor was attached to the right wall of the rectum and the pelvic diaphragm between the anus and the puborectalis. The patient recovered uneventfully and there has not been any evidence of local recurrence for 3 years postoperatively. We consider that abdominoperineal resection may be an appropriate treatment for a large AA infiltrating to the perirectal tissues, because the high recurrence rate of this disease has been attributed to incomplete surgical excision.

Aberrant DNA methylation has been identified as an important mechanism for inactivation of tumor suppressor genes and mismatch repair genes during carcinogenesis. We used bisulfite treatment and the PCR-single strand conformation polymorphism (SSCP) (BiPS) technique to analyze methylation status of the promoter regions of the hMLH1, p16, and HIC1 genes in several cancer cell lines and colorectal cancer tissues. The methylation of the hMLH1, p16 and HIC1 genes was observed in 2, 8, and 13 of 13 cancer cell lines, respectively. The SSCP for p16 and HIC1 in each of the methylation-positive cell lines were similar, indicating relative homogeneity of methylation status and complete methylation in the cell lines. Methylation was observed in 8, 5, and 21 of 25 colorectal cancer tissues for the hMLH1, p16, and HIC1 genes, respectively. The methylated bands revealed by BiPS analysis of the hMLH1 gene were homogeneous, whereas those of the p16 and HIC1 genes were different in each case. The methylation of the promoter region of the HIC1 gene in colorectal cancer was observed most frequently and could serve as a sensitive marker for colorectal cancer. Methylation status of the hMLH1 and p16 gene promoters was correlated with microsatellite instability status, tumor location, and differentiation but not with K-ras mutation or allelic loss of p53.