Prognostic impact of matrix metalloproteinases (MMP-9 and MMP-2) and vascular endothelial growth factor expression in non-small cell lung cancer

To investigate the role of matrix metalloproteinases (MMPs), MMP-9 and MMP-2, and vascular endothelial growth factor (VEGF) in metastasis and their relationship with survival. Early metastasis is the most common cause of lung cancer death. Angiogenesis and basement membrane damage are necessary for growth and invasion of the tumoral cells. VEGF, involved in angiogenic activity, and MMPs, involved in matrix destruction, are important for metastasis in lung cancer. Materials and methods: Using immunohistochemistry analysis, we evaluated MMP-9, MMP-2, and VEGF expressions in paraffin specimens from 91 patients with histopathologically confirmed non-small cell lung cancer and the relationship between MMP-9, MMP-2, and VEGF expressions and the prognosis. Results: For MMP-9 expression, 52 (57.1%) patients were positive and 39 (42.9%) were negative. Patients whose tumors had MMP-9-positive staining had a shorter duration of survival than patients whose tumors had no expression, but it was not statistically significant (14.1 ± 1.7 (median: 12) vs. 16.7 ± 2.2 (median: 15), P > 0.05). For MMP-2 expression, 13 (14.3%) patients were positive and 78 (85.7%) were negative. Patients whose tumors had MMP-2-positive staining had a shorter duration of survival than patients whose tumors had no expression, but it was not statistically significant (12.6 ± 3.6 (median: 8) vs. 16.1 ± 1.5 (median: 14), P > 0.05). For VEGF expression, 34 (37.4%) patients were positive and 57 (62.6%) were negative. There was no significant relationship between the duration of survival for patients whose tumors had VEGF-positive and VEGF-negative staining (15.3 ± 1.7 (median: 18) vs. 15.6 ± 2.1 (median: 13), P > 0.05). Conclusion: Angiogenesis and basement membrane damage are the main components for metastasis, but there was no significant relationship between MMP and VEGF expressions and prognosis. This indicates that the metastasis biology of lung cancer is a complex and multistep pathogenetic mechanism, although a small number of patients were included in our study.

Prognostic impact of matrix metalloproteinases (MMP-9 and MMP-2) and vascular endothelial growth factor expression in non-small cell lung cancer

To investigate the role of matrix metalloproteinases (MMPs), MMP-9 and MMP-2, and vascular endothelial growth factor (VEGF) in metastasis and their relationship with survival. Early metastasis is the most common cause of lung cancer death. Angiogenesis and basement membrane damage are necessary for growth and invasion of the tumoral cells. VEGF, involved in angiogenic activity, and MMPs, involved in matrix destruction, are important for metastasis in lung cancer. Materials and methods: Using immunohistochemistry analysis, we evaluated MMP-9, MMP-2, and VEGF expressions in paraffin specimens from 91 patients with histopathologically confirmed non-small cell lung cancer and the relationship between MMP-9, MMP-2, and VEGF expressions and the prognosis. Results: For MMP-9 expression, 52 (57.1%) patients were positive and 39 (42.9%) were negative. Patients whose tumors had MMP-9-positive staining had a shorter duration of survival than patients whose tumors had no expression, but it was not statistically significant (14.1 ± 1.7 (median: 12) vs. 16.7 ± 2.2 (median: 15), P > 0.05). For MMP-2 expression, 13 (14.3%) patients were positive and 78 (85.7%) were negative. Patients whose tumors had MMP-2-positive staining had a shorter duration of survival than patients whose tumors had no expression, but it was not statistically significant (12.6 ± 3.6 (median: 8) vs. 16.1 ± 1.5 (median: 14), P > 0.05). For VEGF expression, 34 (37.4%) patients were positive and 57 (62.6%) were negative. There was no significant relationship between the duration of survival for patients whose tumors had VEGF-positive and VEGF-negative staining (15.3 ± 1.7 (median: 18) vs. 15.6 ± 2.1 (median: 13), P > 0.05). Conclusion: Angiogenesis and basement membrane damage are the main components for metastasis, but there was no significant relationship between MMP and VEGF expressions and prognosis. This indicates that the metastasis biology of lung cancer is a complex and multistep pathogenetic mechanism, although a small number of patients were included in our study.

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  • Sawicki G, Matsuzaki A, Jankowska-Wieczorek A. Expression of the active form of MMP-2 on the surface of leukemic cells accounts for their in vitro invasion. J Cancer Res Clin Oncol 1998; 124: 245-52.
  • Ohta Y, Watanabe Y. Current concepts of angiogenesis related to primary lung cancer. In: Lung cancer. Pass IH, editor. 2nd ed. Philadelphia (PA): Lippincott Williams-Wilkins; 2000. p.199-210.
  • Robbins SL, Kumar V. Neoplasia. In: Cotran RS, Vinay K, Collins T, Robbins SL, editors. Robbins & Cotran Pathologic basis of disease. 6th ed. Philadelphia (PA): W.B. Saunders Company; 1999. p.301-2.
  • Shou Y, Hirano T, Gong Y, Kato Y, Yoshida K, Ohira T et al. Infl uence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small cell lung cancer. Br J Cancer 2001; 85: 1706-12.
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182-6.
  • Junker K. Prognostic factors in stage I/II non-small cell lung cancer. Lung Cancer 2001; 33: 17-24.
  • Poon RTP, Fan TS, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001; 19: 1207-25.
  • Aikawa H, Takahashi H, Fujimura S, Sato M, Endo C, Sakurada A et al. Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer. Anticancer Res 1999; 19: 4305-10.
  • Ohta Y, Tomita Y, Oda M, Watanabe S, Murakami S, Watanabe Y et al. Tumor angiogenesis and recurrence in stage I non- small cell lung cancer. Ann Th orac Surg 1999; 68: 1034-8.
  • Liao M, Wang H, Lin Z, Feng J, Zhu D. Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer. Lung Cancer 2001; 33: 125-32.
  • Landriscina M, Cassano A, Ratto C, Longo R, Ippoliti M, Palazzotti B et al. Quantitative analysis of basic fi broblast growth factor and vascular endothelial growth factor in human colorectal cancer. Br J Cancer 1998; 78: 765-70.
  • Volm M, Koomagi R, Mattern J. PD-ECGF, bFGF, and VEGF expression in non-small cell lung carcinomas and their association with lymph node metastasis. Anticancer Res 1999; 19: 651-6.
  • Volm M, Mattern J, Koomagi R. Angiostatin expression in non-small cell lung cancer. Clin Cancer Res 2000; 6: 3236-40.
  • Lamoreaux WJ, Fitzgerald MEC, Reiner A, Hasty KA, Charles ST. Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc Res 1998; 55: 29-42.
  • Cox G, Jones JL, Walker RA, Steward WP, O’Byrne KJ. Angiogenesis and non-small cell lung cancer. Lung Cancer 2000; 27: 81-100.
  • Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM et al. Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantifi cative and morphological analyses. Int J Cancer 1997; 72: 556-64.
  • Werner JA, Rathcke IO, Mandic R. Th e role of matrix metalloproteinases in squamous cell carcinomas of the head and neck. Clin Exp Metastas 2002; 19: 275-82.
  • Johansson N, Airola K, Grenman R, Kariniemi AL, Saarialho- Kere U, Kahari VM et al. Expression of collagenase-3 (matrix metalloproteinase-13) in squamous cell carcinomas of the head and neck. Am J Pathol 1997; 151: 499-508.
  • Yoskizaki T, Maruyama Y, Sato H, Furukawa M. Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma. Int J Cancer 2001; 95: 44-50.
  • Bredin CG, Liu Z, Klominek J. Growth factor-enhanced expression and activity of matrix metalloproteases in human non-small cell lung cancer cell lines. Anticancer Res 2003; 23: 5372.
  • Th omas P, Khokha R, Shepherd FA, Feld R, Tsao MS. Diff erential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer. J Pathol 2000; 190: 150-6.
  • Ishikawa S, Takenaka K, Yanagihara K, Miyahara R, Kawano Y, Otake Y et al. Matrix metalloproteinase-2 status in stromal fi broblasts, not in tumor cells, is a signifi cant prognostic factor in non-small-cell lung cancer. Clin Cancer Res 2004; 10: 6579- 85.
  • Hoikkala S, Paakko P, Soini Y, Makitaro R, Kinnula V, Turpeenniemi-Hujanen T. Tissue MMP-2 and MMP-9 are better prognostic factors than serum MMP-2/TIMP-2- complex or TIMP-1 in stage I-III lung carcinoma. Cancer Lett 2006; 236: 125-32.
  • Leinonen T, Pirinen R, Bohm J, Johansson R, Kosma VM. Increased expression of matrix metalloproteinase-2 (MMP-2) predicts tumour recurrence and unfavourable outcome in non- small cell lung cancer. Histol Histopathol 2008; 23: 693-700.
  • Yamamura T, Nakanishi K, Hiroi S, Kumaki F, Sata H, Aida S et al. Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in non-small cell lung carcinomas. Lung Cancer 2002; 35: 249-55.
  • Byun JH, Lee MA, Roh SY, Shim BY, Hong SH, Ko YH et al. Association between cyclooxygenase-2 and matrix metalloproteinase-2 expression in non-small cell lung cancer. Japan J Clin Oncol 2006; 36: 263-8.
  • Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y et al. Th e role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta- analysis. Cancer Invest 2010; 28: 661-9.
  • Leinonen T, Pirinen R, Bohm J, Johansson R, Ropponen K, Kosma VM. Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer. Relation to clinicopathological factors, β-catenin and prognosis. Lung Cancer 2006; 51: 313- 21.
  • Sienel W, Hellers J, Morresi-Hauf A, Lichtinghagen R, Mutschler W, Jochum M et al. Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer. Int J Cancer 2003; 103: 647-51.
  • Cox G, Jones JL, O’Byrne KJ. Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non- small cell lung cancer. Clin Cancer Res 2000; 6: 2349-55.
  • Schutz A, Schneidenbach D, Aust G, Tannapfel A, Steinert M, Wittekind C. Diff erential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung. Tumour Biol 2002; 23: 179-84.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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