Association Between N1IC In Activated Notch1Pathway And The Initiation And Progression Of Breast Cancer

Objective: To explore the significance of N1IC and Snail in the development of breast carcinoma, theprotein expressions of N1IC in activated Notch1signaling pathway and Snail were analyzed in normalcancerous adjacent tissue(NCAT), usual ductal hyperplasia (UDH), ductal carcinoma in situ(DCIS) andinfiltrating ductal carcinoma(IDC), respectively.Methods: Formalin-fixed paraffin-embedded samples from200untreated primary invasive ductalcarcinomas,32ductal carcinomas in situ,40usual ductal hyperplasias and37adjacent non-neoplastictissues were examined. Expressions of N1IC and Snail were measured by immunohistochemistry on tissuemicroarrays to study the difference. The correlations among N1IC, Snail and EMT-related markers werefurther analyzed based on the results of previous research.Results:(1) The percentage of high pression in NCAT, UDH, DCIS and IDC was56.8%,10.0%,65.7%,75.0%for N1IC and43.2%,55.0%,56.3,62.0%for Snail, respectively. A significant difference for theexpression of each studied marker was observed in overall comparison (P<0.05).(2) The results based onclinicopathologic features revealed that the expression of N1IC was significantly associated lymph nodemetastasis in breast cancer patients (P<0.001), and the expression of Snail was significantly associated withlymph node metastasis (P=0.01) and TNM stage (P=0.013).(3) The results on the basis of previous researchshowed that the expression of N1IC consistent with the expression of Notch1during breast canceration wasgradually increased, and the expression of N1IC correlated positively with the expressions of Snail (r=0.143,P=0.044) and N-cadherin(r=0.170, P=0.016) in breast cancer, but inversely correlated with the expression ofE-cadherin (r=-0.507, P<0.001).Conclusions:(1) The expressions of Notch1, N1IC and Snail were gradually increased during breastcanceration, suggesting a potential role in the initiation of breast cancer.(2) High expressions of N1IC andSnail positively associated with lymph node may promote the progression of breast cancer patients.(3)Notch1-N1IC-Snail-EMT signal may play a significant role in the metastasis of breast cancer.