Expression of epidermal growth factor receptor (EGFR) and downstream-activated peptides in surgically excised non-small-cell lung cancer (NSCLC).
Extracellular signal-regulated kinases (ERKs), Akt, and signal transducer and activator of transcription 3 (STAT3) are on signal transduction pathways triggered by epidermal growth factor receptor (EGFR). The purpose of this study was to evaluate the expressions of these peptides and to correlate the level of EGFR expression with downstream-activated peptide expression in non-small-cell lung cancer (NSCLC). A total of 60 specimens were studied by immunohistochemistry. EGFR overexpression was detected in 78% of specimens, but no significant relationship was found between it and any clinicopathological factors investigated. Phosphorylated (p)-ERK, p-Akt, and p-STAT3 expressions were observed in 28, 53, and 58% of specimens, respectively, and p-Akt and p-STAT3 expressions were correlated with well-differentiated tumor (P=0.045 and 0.014, respectively). Half of the 60 specimens expressed two or three downstream-activated peptides. The level of EGFR expression was associated with expressions of p-ERK and p-Akt (P=0.045 and 0.020, respectively). In a preliminary analysis, no peptides examined had an impact on relapse-free survival. In summary, various signal transduction pathways appeared frequently to participate in NSCLC, and the level of EGFR expression appeared to correlate with those of activated ERK and Akt, suggesting some role of receptor overexpression in more potent downstream activation.
Mukohara
Toru
T
First Department of Internal Medicine, Osaka City University School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. toru_mukohara@dfci.harvard.edu
Kudoh
Shinzoh
S
Yamauchi
Setsuko
S
Kimura
Tatsuo
T
Yoshimura
Naruo
N
Kanazawa
Hiroshi
H
Hirata
Kazuto
K
Wanibuchi
Hideki
H
Fukushima
Shoji
S
Inoue
Kiyotoshi
K
Yoshikawa
Junichi
J
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases