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Ann Oncol. 2012 Jul;23(7):1699-705. doi: 10.1093/annonc/mdr552. Epub 2011 Nov 23.

The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer.

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  • 1Department of Hematology and Oncology, Institute of clinical research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main, Germany. albatran@aol.com

Abstract

BACKGROUND:

The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated.

PATIENTS AND METHODS:

We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted.

RESULTS:

In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic.

CONCLUSION:

MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.

PMID:
22112973
[PubMed - indexed for MEDLINE]
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