Phosphorylated GSK3beta-ser9 and EGFR are good prognostic factors for lung carcinomas.
BACKGROUND
Glycogen synthase kinase-3beta (GSK3beta), serine/threonine protein kinase, has been reported to repress the Wnt/beta-catenin pathway and regulate the balance between cellular proliferation and apoptosis. Epithelial growth factor receptor (EGFR) might phosphorylate GSK3beta into inactive phosphorylated GSK3beta-ser9 (P-GSK3beta-ser9).


METHODS
P-GSK3beta-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-GSK3beta-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-GSK3beta-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-GSK3beta-ser9 and EGFR expressions were negatively linked to survival of lung carcinoma patients when stratified according to histological type (p<0.05).


CONCLUSIONS
P-GSK3beta-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.
Zheng
Huachuan
H
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Japan. zheng_huachuan@hotmail.com
Saito
Hiroshi
H
Masuda
Shinji
S
Yang
Xianghong
X
Takano
Yasuo
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011379:Prognosis
D010768:Phosphoserine; D066246:ErbB Receptors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3