A biological staging model for operable non-small cell lung cancer

Cox, G., Jones, J.L., Andi, A., Waller, D.A., & O'Byrne, K.J. (2001) A biological staging model for operable non-small cell lung cancer. Thorax, 56(7), pp. 561-566.

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Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system. Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets. Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC.


A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken. Immunohistochemical analysis was performed on paraffin embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers.


Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)), and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74)) were independent prognostic factors. Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73)) or neither (HR 4.43 (2.29-8.57)) of these markers. EGFR expression correlated with tumour cell MMP-9 expression (p<0.001). Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)).


Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient. The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.

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ID Code: 64908
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Angiogenesis, Matrix metalloproteinases, Non-small cell lung cancer, CD34 antigen, epidermal growth factor receptor, gelatinase A, gelatinase B, paraffin, tyrosine kinase receptor, adult, aged, article, cancer staging, controlled study, female, human, immunohistochemistry, immunoreactivity, lung non small cell cancer, major clinical study, male, molecular biology, oncogene c erb, priority journal, prognosis, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Middle Aged, Multivariate Analysis, Neoplasm Staging, Neovascularization, Pathologic, Receptor, Epidermal Growth Factor, Regression Analysis, Retrospective Studies, Survival Analysis, Tumor Markers, Biological
DOI: 10.1136/thorax.56.7.561
ISSN: 0040-6376
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2001 BMJ Group
Deposited On: 29 Nov 2013 05:05
Last Modified: 17 May 2017 04:51

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