MMP-2 and MMP-9 in lymph-node-positive bladder cancer

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Abstract

Background

Matrix metalloproteinases (MMP), particularly MMP-2 and MMP-9, participate in tumour progression and metastasis in various cancers. Their significance in urothelial cancer of the bladder (UCB) is unclear. Expression analysis of MMP-2 and MMP-9 in tissue microarrays (TMA) constructed of corresponding samples from histopathological normal urothelium, tumour centre and invasion front of primary tumours and lymph-node (LN) metastases might help to elucidate their relevance in UCB.

Method

MMP-2 and MMP-9 expression was evaluated in TMA of 150 surgically treated LN-positive UCB patients. Biomarker expression was correlated with tumour characteristics (primary tumour and LN stage, number, total diameter and extracapsular extension of LN metastases) and overall survival.

Results

While there was a significant increase in MMP-9 expression from normal urothelium over primary tumours to metastases (median scores: 20, 50, 65; p<0.005), no such trend was observed in MMP-2 (median scores: 5, 22, 10; p<0.005). A comparison of expression in the tumour centre and the invasion front showed no difference in both MMP. No association between expression and histopathological tumour characteristics was identified. There was a non-significant trend for a more favourable outcome for patients with high MMP-2 expression in primary tumours.

Conclusion

In LN-positive UCB, MMP-2 and MMP-9 expression was not increased at the invasion front, suggesting an infiltration strategy independent of MMP-2 and MMP-9 activity. Larger series are needed to detect a potential significant trend for favourable outcome in cancers with high MMP-2 expression.

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