Notch3 signaling is associated with MUC5AC expression and favorable prognosis in patients with small intestinal adenocarcinomas

Background: Notch signaling plays diverse roles not only in physiologic processes, including development and differentiation but also in tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross-talk with other signaling pathways. In this study we investigated the expression of Notch3 and MUC proteins and their clinicopathological significance in small intestinal adenocarcinoma (SIAC). Methods: Surgically resected 191 SIACs and their clinical data were collected. Immunohistochemistry for Notch3, MUC2, MUC5AC, and MUC6 using tissue microarrays from formalin-fixed paraffin-embedded normal and matched tumor tissues was performed. Results: Notch3 expression was found in 52 (29.9%) cases of the tumors. MUC2, MUC5AC, and MUC6 were expressed in 52 (27.5%), 51 (31.9%), and 42 (22.0%) cases of the tumor, respectively. Notch3 expression was correlated with the absence of lymphovascular invasion (p = 0.009), lower T stage (p = 0.038), and histological subtype of tubular adenocarcinoma (p = 0.01), respectively. MUC2 was correlated with large tumor size (p = 0.013) and mucinous and signet ring cell adenocarcinomas (p = 0.01). MUC5A was correlated with proximal tumor location (p< 0.0001) and tumor differentiation (p = 0.027). MUC6 was correlated with proximal tumor location (p< 0.0001) and lower pT stage (p = 0.009), and absence of lymphovascular invasion, respectively. A significant correlation was noted between Notch3 and MUC5AC expression (p = 0.019). Notch3 expression was a relatively favorable prognostic factor in SIACs by univariate (p = 0.05) and multivariate analysis (p = 0.08, Cox Hazard ratio 0.841). Conclusion: Our findings indicate that Notch3 signaling, associated with MUC5AC expression, could be a more favorable prognostic factor in SIACs.