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Comparative Study
. 2004 Mar 8;90(5):1047-52.
doi: 10.1038/sj.bjc.6601644.

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

S Vicent  1 , J M López-Picazo, G Toledo, M D Lozano, W Torre, C Garcia-Corchón, C Quero, J-C Soria, S Martín-Algarra, R G Manzano, L M Montuenga
Affiliations
Comparative Study

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

S Vicent et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of normal lung and NSCLC specimens with a specific antibody against P-ERK: (A) normal alveolar epithelium, negative staining; (B) normal bronchiolar epithelium, negative staining; (C) squamous cell carcinoma, negative staining; (D) adenocarcinoma with nuclear P-ERK staining; (E) squamous cell carcinoma with cytoplasmic and moderate nuclear staining; (F) adenocarcinoma with nuclear and extensive cytoplasmic staining.
Figure 2
Figure 2
Kaplan–Meier survival plot by cytoplasmic P-ERK expression (15% cutoff). Survival plot of all patients.
See this image and copyright information in PMC

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