ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours.
Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours.
Vicent
S
S
Carcinogenesis Unit, Division of Oncology, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain.
López-Picazo
J M
JM
Toledo
G
G
Lozano
M D
MD
Torre
W
W
Garcia-Corchón
C
C
Quero
C
C
Soria
J-C
JC
Martín-Algarra
S
S
Manzano
R G
RG
Montuenga
L M
LM
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; 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 / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008479:Mediastinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009367:Neoplasm Staging; D010766:Phosphorylation
D019394:Ki-67 Antigen; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases