Genetic instability of stromal cells in ulcerative colitis-associated carcinogenesis

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To know roles of genetic instability of stromal cells on carcinogenesis in ulcerative colitis (UC), microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in epithelial and stromal cells separated by microdissection, by using PCR-SSCP method. In sporadic colon cancers, MSI positive results were obtained for both epithelium and stromal tissue. While MSI in epithelium correlated with differentiation and Dukes' stage, that in stroma demonstrated an inverse correlation, being particularly frequent in well differentiated adenocarcinomas and Dukes' A lesions, suggesting an alternative pathway of carcinogenesis involving stromal genetic instability in the development of colon cancers. In contrast, although chromosome 17-MSI and -LOH in epithelium correlated with histological progression, in stroma they showed a consistently high frequency throughout the different stages, indicating a distinct carcinogenesis pathway of UC.