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Imaging, Diagnosis, Prognosis |
Departments of 1 Cardio-Thoracic Surgery and 2 Paediatrics; 3 Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle; and 4 Cancer Center and Division of Pediatric Hematology/Oncology, Munich University of Technology, Munich, Germany
Requests for reprints: Hans Stefan Hofmann, Department of Cardio-Thoracic Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 4, 06097 Halle, Germany. Phone: 49-345-557-2793; Fax: 49-345-557-2802; E-mail: stefan.hofmann{at}medizin.uni-halle.de.
Purpose: Non–small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix.
Experimental Design: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLC patients. Validation of microarray results was done using reverse transcription-PCR and immunohistology.
Results: MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse–free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells.
Conclusions: MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
Key Words: NSCLC • MMP-12 • local recurrence • metastasis • DNA array
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