Altered Distribution of -Catenin, and Its Binding

pression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal #-catenin expression was more closely linked to APC alterations in sporadic cancers than in UCrelated cancers. These data suggest that alterations of the #-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of #-catenin, E-cadherin, and APC between UCrelated and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups. KEY WORDS: APC, #-catenin, Colorectal cancer, E-cadherin, Immunohistochemistry, Ulcerative colitis. Mod Pathol 2001;14(1):29--39 #-catenin is a multifunctional protein that is involved in cell-- cell interaction and transcriptional signaling (1--5). #-catenin expression is largely regulated by its two major binding partners, E-cadherin on the membrane and the adenomatous polyposis coli (APC) protein i

Chromosomal Alterations in Ulcerative Colitis-Related and Sporadic Colorectal Cancers by Comparative Genomic Hybridization

Both ulcerative colitis (UC)-related and sporadic colorectal cancers are thought to evolve through a multistep process of genomic instability, accumulation of genomic alterations and clonal expansion. This process may involve different genomic changes in UC-related cancers than in sporadic cancers due to the origin of UC-related cancers in an inflammatory field. This study was designed to define the specific genomic events in UC-related cancers. Comparative genomic hybridization (CGH) was performed on 32 UC-related and 42 stage-matched sporadic colorectal cancers. The mean number of chromosomal alterations per case was similar in the UC-related and sporadic tumor groups (8.6 in UC, 8.1 in sporadic). Frequently lost regions in both cancer groups were 18q (78% UC, 69% sporadic), 8p (53% UC, 50% sporadic), and 17p (44% UC, 57% sporadic). The three most frequent gains involved chromosomes 8q (63% UC, 45% sporadic), 20q (44% UC, 67% sporadic), and 13q (44% UC, 38% sporadic). Chromosome 5q was lost in 56% of UC-related but in only 26% of sporadic cancers. Losses of 17q and gains of 5p were also more frequent in UC-related cancers, whereas losses of 14q and gains of Xp were significantly less common in UC-related cancers than in sporadic tumors. There was a stage-related increase in chromosome 8 alterations in UC-related but not in sporadic cancers, while only sporadic tumors showed a stage progression for 5p loss, 17q gain, and 18q loss. Thus, differences in the frequency and timing of individual chromosomal alterations suggest that the genetic pathways in these two tumor groups are distinct from each other.