Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients.
OBJECTIVE
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.


METHODS
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.
Hofmann
Hans-Stefan
HS
Department of Cardio-Thoracic Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 4, 06097 Halle, Germany. stefan.hofmann@medizin.uni-halle.de
Hansen
Gesine
G
Richter
Günther
G
Taege
Christiane
C
Simm
Andreas
A
Silber
Rolf-Edgar
RE
Burdach
Stefan
S
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D012334:RNA, Neoplasm; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12