Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer.

Background/Aim: Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes. Materials and Methods: Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis. Results: Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident. Conclusion: Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.