Phosphorylated GSK3β-ser⁹ and EGFR are Good Prognostic Factors for Lung Carcinomas

Abstract

Background: Glycogen synthase kinase-3β (GSK3β), serine/threonine protein kinase, has been reported to repress the Wnt/β-catenin pathway and regulate the balance between cellular proliferation and apoptosis. Epithelial growth factor receptor (EGFR) might phosphorylate GSK3β into inactive phosphorylated GSK3β-ser⁹ (P-GSK3β-ser⁹). Patients and Methods: P-GSK3β-ser⁹ and EGFR expressions were examined on tissue microarrays (TMA) of lung carcinoma (n=154) by immunohistochemistry and compared with clinicopathological parameters of the tumors, including the expression of Ki-67 and phosphatase and tensin homology deleted from human chromosome 10 (PTEN), as well as survival data. Results: The P-GSK3β-ser⁹ expression was highest in adenocarcinoma (AD) and lowest in small cell carcinomas (SCC), compared with other types of lung carcinoma (p<0.05). Its expression was negatively correlated with PTEN and Ki-67 expression (p<0.05), but not with age, gender, pleural invasion, lymphatic or venous invasion, lymph node metastasis or Union Internationale Contre le Cancer (UICC) staging (p>0.05). EGFR was strongly expressed in squamous carcinomas (SQ), compared with other types of lung carcinomas. Its expression was also positively correlated with lymphatic and venous invasion and P-GSK3β-ser⁹ expression, and negatively with the PTEN expression of the tumors (p<0.05), but not with the age, gender, pleural invasion, lymph node metastasis, or UICC staging (p>0.05). Kaplan-Meier analysis indicated that P-GSK3β-ser⁹ and EGFR expressions were negatively linked to survival of lung carcinoma patients when stratified according to histological type (p<0.05). Conclusion: P-GSK3β-ser⁹ and EGFR are involved in the histogenesis of different lung carcinomas. Their overexpression might result from PTEN loss and can be considered as markers of worse prognosis in lung carcinoma patients.