This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishikawa, S. Articles by Tanaka, F. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, S. Articles by Tanaka, F.

Matrix Metalloproteinase-2 Status in Stromal Fibroblasts, Not in Tumor Cells, Is a Significant Prognostic Factor in Non–Small-Cell Lung Cancer

¹ Department of Thoracic Surgery, Kyoto University, Faculty of Medicine, Kyoto; ² Second Department of Surgery, Faculty of Medicine, Kagawa University, Kita-gun; ³ Department of Translational Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto; and ⁴ Department of Thoracic Surgery, Seishin-Iryo Center Hospital, Kobe, Japan

Purpose: The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non–small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression.

Experimental Design: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I–IIIA, NSCLC.

Results: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor.

Conclusions: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC.

This article has been cited by other articles:

				G. A. Alyahya, M. Kolko, J. U. Prause, B. S. Nielsen, J. Wang, and S. Heegaard Matrix Metalloproteinase-2 Is Expressed in Melanoma-Associated Spongiform Scleropathy Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2806 - 2811. [Abstract] [Full Text] [PDF]

				G. P. Cosgrove and R. M. du Bois Matrix Metalloproteinase-7 Expression in Fibrosing Lung Disease: Restoring the Balance Chest, May 1, 2008; 133(5): 1058 - 1060. [Full Text] [PDF]

				K. Ueda, M. Jinbo, T.-S. Li, T. Yagi, K. Suga, and K. Hamano Computed Tomography-Diagnosed Emphysema, Not Airway Obstruction, Is Associated with the Prognostic Outcome of Early-Stage Lung Cancer. Clin. Cancer Res., November 15, 2006; 12(22): 6730 - 6736. [Abstract] [Full Text] [PDF]

				J. Xu, A. L. Mora, J. LaVoy, K. L. Brigham, and M. Rojas Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L658 - L667. [Abstract] [Full Text] [PDF]

				C-Q Zhu, W Shih, C-H Ling, and M-S Tsao Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J. Clin. Pathol., August 1, 2006; 59(8): 790 - 800. [Abstract] [Full Text] [PDF]

				J. H. Byun, M. A. Lee, S. Y. Roh, B. Y. Shim, S. H. Hong, Y. H. Ko, S. J. Ko, I. S. Woo, J. H. Kang, Y. S. Hong, et al. Association between Cyclooxygenase-2 and Matrix Metalloproteinase-2 Expression in Non-Small Cell Lung Cancer Jpn. J. Clin. Oncol., May 1, 2006; 36(5): 263 - 268. [Abstract] [Full Text] [PDF]