Expression of Notch 1 and 3 is related to inhibition of lymph node metastasis and progression in non-small cell lung carcinomas

Background and aims: Notch signaling pathways are well known for their major role in stem cell differentiation. However, varied results have been reported in relation to their oncogenic role, depending on tumor type. We studied the expression of Notch receptors and other cell cycle proteins in human non-small cell lung carcinomas (NSCLC) and analyzed their relationship to tumor progression. Methods: We examined the tissue microarrays of 158 cases of NSCLC for Notch1 and 3, and cell cycle regulatory proteins p53, p16INK4a, pRb and CDK2 by immunohistochemistry. Results: Notch1 and 3 receptors were noted in 81.6% and 79.7% of cases, respectively. Notch1 expression was negatively correlated with lymph node metastasis (P = 0.043) and Notch3 was negatively correlated with more advanced pathologic T stage (P = 0.024). However, expressions of Notch receptors didn't show any significant prognostic value for NSCLC. Of the cell cycle proteins, CDK2 and pRb were negatively correlated with Notch1 (P = 0.013) and Notch3 (P = 0.018). Conclusions: Notch receptors play an inhibitory role in metastasis to lymph node and in the activity of cell cycle proteins, which may lead to suppression of NSCLC.