Activated Akt expression has significant correlation with EGFR and TGF-alpha expressions in stage I NSCLC.
BACKGROUND
In vitro studies have indicated that epidermal growth factor receptor (EGFR) may intensify signaling output by the receptor's overexpression, heterodimerization with HER-2, or autocrine expression of ligands. The purpose of the present study was to evaluate the correlation between EGFR and its related proteins and to explore the prognostic value of the proteins.


METHODS
Immunohistochemical staining of transforming growth factor alpha (TGF-alpha), EGFR, HER-2, and phosphorylated (p-)Akt was performed in specimens surgically excised from 91 consecutive patients with p-stage I non-small cell lung cancer (NSCLC). Expression or coexpression of TGF-alpha and the receptors were related to expression of p-Akt. The prognostic impact of these peptides was also tested.


RESULTS
TGF-alpha, EGFR and HER-2 overexpressions were detected in 32%, 79% and 13% of tumors, respectively. Coexpressions of TGF-alpha & EGFR and EGFR & HER-2 were observed in 29% and 11% of tumors, respectively. P-Akt expression was found in 73% of tumors. Significant correlations between EGFR TGF-alpha or coexpression of TGF-alpha & EGFR and p-Akt expression were found (p=0.006, 0.008 and 0.010, respectively). No proteins examined had an impact on relapse-free survival.


CONCLUSIONS
The Akt pathway is frequently involved in NSCLC and overexpression of EGFR and autocrine expression of TGF-alpha may increase the potency of Akt activation.
Mukohara
Toru
T
First Department of Internal Medicine, Osaka City University School of Medicine, Osaka, Japan. toru_mukohara@dfci.harvard.edu
Kudoh
Shinzoh
S
Matsuura
Kuniomi
K
Yamauchi
Setsuko
S
Kimura
Tatsuo
T
Yoshimura
Naruo
N
Kanazawa
Hiroshi
H
Hirata
Kazuto
K
Inoue
Kiyotoshi
K
Wanibuchi
Hideki
H
Fukushima
Shoji
S
Yoshikawa
Junichi
J
D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*
D011518:Proto-Oncogene Proteins; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt