Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis

Anja Rabien,Wilko Weichert,Ergin Kilic,Kurt Miller,Glen Kristiansen,Klaus Jung,Carsten Stephan,Andreas Erbersdobler

doi:10.1186/1479-5876-11-258

Abstract

BackgroundMatrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study.MethodsTumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray.ResultsRECK strongly decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon signed rank test, P < 0.001), and it discriminated tumor entities showing the highest expression in oncocytomas. EMMPRIN, however, could be significantly correlated to pT stage and Fuhrman grading (Spearman’s correlation coefficient rs = 0.289 and rs = 0.382, respectively). Higher expression of EMMPRIN was associated with decreased overall survival in Kaplan-Meier analysis (P < 0.001), and the EMMPRIN level could independently predict survival for cases without metastasis and involvement of lymph nodes. Decreased RECK expression was confirmed by Western blotting in tissue of eight normal/tumor matches of patients after radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous.ConclusionsWe propose RECK down regulation in renal cell carcinoma to be an early event that facilitates tumor formation and progression. EMMPRIN, however, as a prognostic tumor marker, increases only when aggressiveness is proceeding and could add an additional step to invasive properties of renal cell carcinoma.

Highlights

Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis
In renal cell carcinoma (RCC) which represent the majority of 85-90% of kidney neoplasms [2,3], survival is mostly determined by distal metastases detected in 30% of the patients even at the
In search for new, more useful biomarkers to diagnose RCC or to improve prognosis we aimed to determine thebalance of an endogenous inhibitor of matrix metalloproteinases (MMPs) and an inducer of MMPs, namely reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN, CD147), which we have shown to be responsible for a dysbalance in urothelial carcinoma of the bladder [6]

Summary

Introduction

Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study. In renal cell carcinoma (RCC) which represent the majority of 85-90% of kidney neoplasms [2,3], survival is mostly determined by distal metastases detected in 30% of the patients even at the Variable Cases (n / %).

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