Loss of Smad signaling in @entity1 @entity14 is associated with XXXX and poor prognosis.

@entity1 @entity5 @entity2536 @entity1442 @entity2533 @entity14 @entity1594 @entity3
PURPOSE: Based largely on in vitro investigations and animal studies, investigators believe that disruptions of @entity2533 ( @entity2533 ) signaling contribute to the development and progression of @entity1 @entity14 . The purpose of this study was to directly assess the status of the @entity2533 signaling pathway in @entity14 and determine the effects of its disruption on clinical behavior and outcome. MATERIALS AND METHODS: Smad proteins are the principal intracellular components of the @entity2533 signaling pathway. We conducted a high-throughput analysis of the expression patterns of @entity2536 , phosphorylated (activated) @entity2536 (pSmad2), and @entity1594 in more than 600 @entity1 @entity14 specimens assembled in tissue microarrays. RESULTS: The vast majority (93.8%; 95% CI: 92%-96%) of @entity14 expressed phosphorylated @entity2536 , indicating the ability of the @entity5 to survive and proliferate within a microenvironment that contains bioactive @entity2533 . Twelve of 633 (1.9%; 95% CI: 1%-3%) cases failed to express @entity2536 , and 15 of 641 (2.3%; 95% CI: 1%-4%) cases failed to express @entity1594 . Moreover, 29 of 615 (4.7%; 95% CI: 3%-7%) of cases expressed @entity2536 but not its activated form (pSmad2), suggesting the presence of a @entity2533 receptor defect. Based on an analysis of 577 cases for which clinical outcome information was available, failure to express @entity2536 , pSmad2, or @entity1594 was associated with @entity5 , the presence of lymph node @entity3 , and a significantly shorter overall survival (median survival: 35 vs 58 months). DISCUSSION: Loss of Smad activation and/or expression occurs in approximately 10% of @entity14 . This subset has a poor prognosis because of its association with @entity1442 and the presence of lymph node @entity3 at diagnosis.
