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.
July 2001
Thorax;Jul2001, Vol. 56 Issue 7, p561
Academic Journal
Background-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 metallonroteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC. Methods--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 makers. Results--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)). Conclusion--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.


Related Articles

  • RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis. Tsuta, K; Kohno, T; Yoshida, A; Shimada, Y; Asamura, H; Furuta, K; Kushima, R // British Journal of Cancer;3/11/2014, Vol. 110 Issue 6, p1571 

    Background:To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors.Methods:We investigated 1874 patients with carcinomas, including...

  • Mechanistic insights into the activation of oncogenic forms of EGF receptor. Wang, Zhihong; Longo, Patti A; Tarrant, Mary Katherine; Kim, Kwangsoo; Head, Sarah; Leahy, Daniel J; Cole, Philip A // Nature Structural & Molecular Biology;Dec2011, Vol. 18 Issue 12, p1388 

    Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly activated by mutation in non-small cell lung cancer. The mechanism of this oncogenic activation is not completely understood, but in contrast to that of the wild-type EGFR, it is proposed to be independent of...

  • Effect of Src Tyrosine Kinase Inhibition on Secretion of MMP-2 and MMP-9 by Non-small Cell Lung Cancer Cells. Rui ZHENG; Xiaosong QIN; Wenjie LI; Jian KANG // Chinese Journal of Lung Cancer;Jan2011, Vol. 14 Issue 1, p13 

    Background and objective Src tyrosine kinase and matrix metalloproteinase play the pivotal roles in lung cancer invasion and metastasis. The aim of this study is to evaluate the effect of Src tyrosine kinase inhibition on secretion of matrix metalloproteinase 2 (MMP-2) and matrix...

  • ADAM12-cleaved ephrin-A1 contributes to lung metastasis. Ieguchi, K; Tomita, T; Omori, T; Komatsu, A; Deguchi, A; Masuda, J; Duffy, S L; Coulthard, M G; Boyd, A; Maru, Y // Oncogene;4/24/2014, Vol. 33 Issue 17, p2179 

    Eph receptor tyrosine kinases and their ephrin ligands have been implicated in neuronal development and neovascularization. Overexpression of ephrin-A1 has been implicated in tumor progression and poor prognosis. However, the mechanisms are not clear. Here, we report a role of the Eph/ephrin...

  • Non-Small Cell Lung Cancer beyond Biomarkers: The Evolving Landscape of Clinical Trial Design. Dimou, Anastasios; Papadimitrakopoulou, Vassiliki // Journal of Personalized Medicine;Sep2014, Vol. 4 Issue 3, p386 

    The approval of EGFR and ALK directed tyrosine kinase inhibitors materialized the concept of tailoring therapy on the basis of specific biomarkers for treating patients with NSCLC. Research for other biologics, although demonstrating clinical benefit, has been less successful so far for...

  • Sorafenib and Sunitinib in the Treatment of Advanced Non-Small Cell Lung Cancer. Gridelli, Cesare; Maione, Paolo; Del Gaizo, Filomena; Colantuoni, Giuseppe; Guerriero, Ciro; Ferrara, Carmine; Nicolella, Dario; Comunale, Daniela; De Vita, Alba; Rossi, Antonio // Oncologist;Feb2007, Vol. 12 Issue 2, p191 

    Despite the optimization of chemotherapy regimens, treatment outcomes for advanced non-small cell lung cancer (NSCLC) are still considered to be disappointing. Thus, clinical research of new treatment strategies is warranted. Several targeted agents have been introduced into clinical trials in...

  • Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. P. A. Zucali; M. G. Ruiz; E. Giovannetti; A. Destro; M. Varella-Garcia; K. Floor; G. L. Ceresoli; J. A. Rodriguez; I. Garassino; P. Comoglio; M. Roncalli; A. Santoro; G. Giaccone // Annals of Oncology;Sep2008, Vol. 19 Issue 9, p1605 

    Background: Approximately 10% of unselected non-small-cell lung cancer (NSCLC) patients responded to the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, resistance mechanisms are not well understood. We evaluated several potential biological markers of...

  • Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer. Cappuzzo, Federico; Magrini, Elisabetta; eresol, Giovanni Luca; Bartolini, Stefania; Rossi, Elisa; Ludovini, Vienna; Gregorc, Vanesa; Ligorio, Claudia; Cancellieri, Alessandra; Damiani, Stefania; Spreafico, Anna; Paties, Carlo Terenzio; Lombardo, Laura; Calandri, Cesare; Bellezza, Guido; Tonato, Maurizio; Crinò, Lucio // JNCI: Journal of the National Cancer Institute;8/4/2004, Vol. 96 Issue 15, p1133 

    Background: Gefitinib, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has activity against approximately 10% of unselected non-small-cell lung cancer (NSCLC) patients. Phosphatidylinositol 3'kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), the...

  • Insulin-like growth factor-1 receptor (IGF-1R) as a biomarker for resistance to the tyrosine kinase inhibitor gefitinib in non-small cell lung cancer. Peled, Nir; Wynes, Murry; Ikeda, Norihiko; Ohira, Tatsuo; Yoshida, Koichi; Qian, Jin; Ilouze, Maya; Brenner, Ronen; Kato, Yasufumi; Mascaux, Celine; Hirsch, Fred // Cellular Oncology (2211-3428);Jul2013, Vol. 36 Issue 4, p277 

    Background: The insulin-like growth factor-1 receptor (IGF-1R) pathway is known to play a role in the acquisition of resistance to epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, its exact role in TKI resistance...


Read the Article


Sign out of this library

Other Topics