Amyloid precursor protein and its phosphorylated form in non-small cell lung carcinoma

Amyloid precursor protein (APP) is a well-known to be involved in the development of Alzheimer's disease and harbors several phosphorylation sites in its cytoplasmic domain. APP has been also proposed as one of the molecules involved in cell proliferation and invasion in several human malignancies. However, the roles of APP including its phosphorylated form (p-APP) have remained largely unexplored in non-small cell lung carcinoma (NSCLC). Therefore, in this study, we first examined both APP and p-APP expressions and then explored the association between p-APP/APP status and clicopathological parameters in NSCLC. The number of APP-positive cases was 24/91 (26%) in adenocarcinomas (Ad) and 16/35 (46%) in squamous cell carcinomas (Sq), respectively. p-APP-positive cases in Ad and Sq were 28 (31%) and 17 (49%), respectively. In Ad cases, both APP and p-APP were significantly associated with clinical stages (APP and p-APP), pathologic T (p-APP), and pathologic N (APP and p-APP) of the cases examined. In Sq cases, there were no significant associations between APP status and any of the clinicopathological parameters examined with an exception of the significant correlation of p-APP with lymphatic invasion. APP status was not significantly associated with overall survival (OS) of Ad patients but a significant association was detected between p-APP-positive cases and OS of these patients (p < 0.0001). In Sq cases, both APP- (p = 0.01) and p-APP-positive (p = 0.04) groups were also significantly associated with adverse clinical outcome. These results did firstly demonstrate that APP, in particular, p-APP, is considered a potent prognostic factor for both Ad and Sq lung carcinoma patients. However, APP signaling including its phosphorylation signal are considered different between these two types of NSCC cells and further investigations are required for clarification.