Frequent activation of mammalian target of rapamycin in primary lung adenocarcinoma and preinvasive lesion

Abstract

Background and aim: The mammalian target of rapamycin (mTOR) pathway is important for cell survival, growth and proliferation and may be involved in the histological progression of lung adenocarcinoma (AC). Methods: We compared the expression of the mTOR signal pathway molecules, i.e., phosphorylated m-TOR (p-mTOR), phosphatase and tensin homolog deleted on chromosome ten (PTEN), epidermal growth factor receptor (EGFR), and cyclin D1, among lung AC, adenocarcinoma in situ (AIS) including both pure bronchioloalveolar carcinoma (BAC) and peripheral BAC-like lesions around invasive carcinoma, atypical adenomatous hyperplasia (AAH), and normal parenchyma surrounding tumor by immunohistochemistry. The protein expression was also correlated with patients’ clinicopathological data on smoking history, tumor stage at diagnosis, recurrence and survival. Results: Intermediate or strong immunoreactivity for p-mTOR was seen in 84.1% of AC and 90.2% of AIS. Partial or complete loss of PTEN was demonstrated in 88.8% of AC and 30.4% of AIS. A significant trend of increasing EGFR, loss of PTEN, p53 expression and Ki-67 labeling index were observed by histological progression from AAH to invasive AC through AIS. Expression of p-mTOR was associated with smoking status. Conclusions: Activation of mTOR can occur by various stimuli and may be an early event in the carcinogenesis of lung AC, and may be associated with sex and smoking status of the patient.