Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis.

摘要: High-level microsatellite instability (AISI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and most presenting In the inherited condition hereditary nonpolyposis cancer (HNPCC). Distinction between these categories MSI-H clinical importance aim this study was assess clinical, pathological, molecular features that might he discriminatory. One hundred twelve from families fulfilling Bethesda criteria were compared with 57 cancers. HNPCC presented at a lower age (P < 0.001) no being diagnosed before years. MSI less extensive 72% markers showing band shifts 87% tumors 0.001). Absent immunostaining for hMSH2 only found tumors. Methylation bMLH1 observed but also 55% showed loss expression hMLH1 = 0.02). more frequently characterized by aberrant beta -catenin as evidenced nuclear positivity Aberrant p53 infrequent both groups. There differences respect 5q heterozygosity or codon 12 K-ras mutation, which Sporadic heterogeneous 0.001), poorly differentiated 0.02), mucinous proximally located 0.04) than RNPCC cancers, contiguous adenomas likely be serrated whereas traditional dominant HNPCC. Lymphocytic infiltration pronounced results did not reach statistical significance. Overall, like common terms morphology displayed consistent different morphogenesis. No individual feature discriminatory all RN-PCC However, model based on four able classify 94.5% The finding multiple familial genotype phenotype tumorigenesis through parallel evolutionary pathways emphasizes studying two groups separately.