Microsatellite instability in XXXX of the biliary tract.

@entity6756 @entity4929 @entity5 @entity9736 @entity201 @entity420 @entity1125
Intraductal @entity4929 of the biliary tree are unusual lesions characterized by solitary or diffuse growth along the intra- and/or extrahepatic biliary tract. @entity1125 bear some clinicopathologic similarity to @entity4929 of the pancreas. Like @entity4929 of the pancreas, @entity1125 can be purely intraductal lesions or can give rise to invasive @entity420 . We recently studied the genetic alterations present in a series of @entity1125 and noted the presence of allelic shifts in some @entity5 during allelic loss assays on chromosomes 5q and 18q. This suggested that microsatellite instability might play a role in the molecular pathogenesis of @entity1125 . Genomic DNA was extracted from 17 @entity4929 , 6 associated invasive @entity201 , and corresponding normal tissues, and microsatellite instability testing was performed using the 5 microsatellite loci recommended by the 1997 National @entity5 Institute-sponsored consensus conference (D2S123, D5S346, D17S250, Bat-25, and Bat-26). High-level microsatellite instability was considered to be present when at least two of five microsatellite loci showed allelic shifts, and low-level microsatellite instability, when only one locus was shifted, as per the National @entity5 Institute criteria. We also determined the methylation status of the DNA mismatch repair gene @entity6756 by @entity9736 treatment of genomic DNA, followed by methylation-specific PCR. High-level microsatellite instability was present in 2 of 17 (11.8%) @entity1125 , including 1 case of purely intraductal @entity5 and 1 case with both intraductal and invasive @entity201 components. In both cases there was extensive microsatellite instability, with allelic shifts in five of five and four of five microsatellite markers, respectively. Low-level microsatellite instability was present in 6 of 17 (35.3%) @entity1125 , including 2 cases of purely intraductal @entity5 and 4 cases with both intraductal and invasive @entity201 components. Interestingly, the pattern of allelic shifts was frequently not identical between the intraductal and invasive @entity201 components; although the same microsatellite markers were shifted, alleles of differing lengths were generated in the intraductal and invasive components of the @entity5 with high-level microsatellite instability and of two @entity5 with low-level microsatellite instability. None of the @entity1125 (0 of 10 cases with adequate DNA for evaluation) showed methylation of @entity6756 . These results indicate that microsatellite instability is a relatively frequent event in @entity4929 of the biliary tree but is not associated with @entity6756 promoter hypermethylation. The finding that alleles of differing lengths were frequently generated between the intraductal and invasive components of those @entity5 with microsatellite instability suggests that there is significant genetic heterogeneity within these @entity5 .
