Thorax 2001;56:561-566 ( July )

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

G Cox^{a b}, J L Jones^c, A Andi^a, D A Waller^b, K J O'Byrne^a

^a Department of Medical Oncology, Leicester Royal Infirmary, Leicester LE1 5WW, UK, ^b Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, Leicester LE3 9QP, UK, ^c Department of Pathology, Glenfield Hospital

Correspondence to: Dr K J O'Byrne KOByrne{at}uhl.trent.nhs.uk

Received 24 August 2000; Returned to authors 18 December 2000; Revised version received 14 March 2001; Accepted for publication 19 March 2001

BACKGROUNDCurrently 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.
METHODSA 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.
RESULTSTumour 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)).
CONCLUSIONAngiogenesis, 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.


Keywords: angiogenesis; matrix metalloproteinases; non-small cell lung cancer

---

© 2001 by Thorax
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Kawachi, R., Nakazato, Y., Takei, H., Koshi-ishi, Y., Goya, T. (2009). Clinical significance of preoperative carcinoembryonic antigen level for clinical stage I non-small cell lung cancer: can preoperative carcinoembryonic antigen level predict pathological stage?. ICVTS 9: 199-202 [Abstract] [Full Text]  
• Zhu, C-Q, Shih, W, Ling, C-H, Tsao, M-S (2006). Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation.. J. Clin. Pathol. 59: 790-800 [Abstract] [Full Text]  
• Guo, J., Higashi, K., Ueda, Y., Oguchi, M., Takegami, T., Toga, H., Sakuma, T., Yokota, H., Katsuda, S., Tonami, H., Yamamoto, I. (2006). Microvessel Density: Correlation with 18F-FDG Uptake and Prognostic Impact in Lung Adenocarcinomas. JNM 47: 419-425 [Abstract] [Full Text]  
• Nakamura, H, Kawasaki, N, Taguchi, M, Kabasawa, K (2006). Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis. Thorax 61: 140-145 [Abstract] [Full Text]  
• Acuff, H. B., Carter, K. J., Fingleton, B., Gorden, D. L., Matrisian, L. M. (2006). Matrix Metalloproteinase-9 from Bone Marrow-Derived Cells Contributes to Survival but not Growth of Tumor Cells in the Lung Microenvironment. Cancer Res. 66: 259-266 [Abstract] [Full Text]  
• Dong, B., Sato, M., Sakurada, A., Sagawa, M., Endo, C., Wu, S., Yamanaka, S., Horii, A., Kondo, T. (2005). Computed tomographic images reflect the biologic behavior of small lung adenocarcinoma: They correlate with cell proliferation, microvascularization, cell adhesion, degradation of extracellular matrix, and K-ras mutation. J. Thorac. Cardiovasc. Surg. 130: 733-739 [Abstract] [Full Text]  
• Jiang, F., Caraway, N. P., Nebiyou Bekele, B., Zhang, H.-Z., Khanna, A., Wang, H., Li, R., Fernandez, R. L., Zaidi, T. M., Johnston, D. A., Katz, R. L. (2005). Surfactant Protein A Gene Deletion and Prognostics for Patients with Stage I Non-Small Cell Lung Cancer. Clin. Cancer Res. 11: 5417-5424 [Abstract] [Full Text]  
• Fong, K M, Sekido, Y, Gazdar, A F, Minna, J D (2003). Lung cancer * 9: Molecular biology of lung cancer: clinical implications. Thorax 58: 892-900 [Abstract] [Full Text]  
• Poleri, C., Morero, J. L., Nieva, B., Vazquez, M. F., Rodriguez, C., de Titto, E., Rosenberg, M. (2003). Risk of Recurrence in Patients With Surgically Resected Stage I Non-small Cell Lung Carcinoma: Histopathologic and Immunohistochemical Analysis. Chest 123: 1858-1867 [Abstract] [Full Text]  
• Swinson, D. E.B., Jones, J. L., Richardson, D., Wykoff, C., Turley, H., Pastorek, J., Taub, N., Harris, A. L., O'Byrne, K. J. (2003). Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non-Small-Cell Lung Cancer. JCO 21: 473-482 [Abstract] [Full Text]  
• Spiro, S. G., Porter, J. C. (2002). Lung Cancer--Where Are We Today?: Current Advances in Staging and Nonsurgical Treatment. Am. J. Respir. Crit. Care Med. 166: 1166-1196 [Abstract] [Full Text]  
• Herbst, R. S., Maddox, A.-M., Rothenberg, M. L., Small, E. J., Rubin, E. H., Baselga, J., Rojo, F., Hong, W. K., Swaisland, H., Averbuch, S. D., Ochs, J., LoRusso, P. M. (2002). Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non-Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial. JCO 20: 3815-3825 [Abstract] [Full Text]  
• Brundage, M. D., Davies, D., Mackillop, W. J. (2002). Prognostic Factors in Non-small Cell Lung Cancer* : A Decade of Progress. Chest 122: 1037-1057 [Abstract] [Full Text]  
• Marchetti, A., Tinari, N., Buttitta, F., Chella, A., Angeletti, C. A., Sacco, R., Mucilli, F., Ullrich, A., Iacobelli, S. (2002). Expression of 90K (Mac-2 BP) Correlates with Distant Metastasis and Predicts Survival in Stage I Non-Small Cell Lung Cancer Patients. Cancer Res. 62: 2535-2539 [Abstract] [Full Text]