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

Journal of Translational Medicine

Andreas Erbersdobler⁴  Klaus Jung⁶  Kurt Miller³  Glen Kristiansen¹  Wilko Weichert⁵  Ergin Kilic²  Carsten Stephan⁶  Anja Rabien³ 

[1] Institute of Pathology, University Hospital of Bonn, Bonn, Germany;Institute of Pathology, Charité – Universitätsmedizin Berlin, Berlin, Germany;Department of Urology, Research Division, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany;Institute of Pathology, University of Rostock, Rostock, Germany;Institute of Pathology, University of Heidelberg and National Center of Tumor Diseases (NCT), Heidelberg, Germany;Berlin Institute for Urologic Research, Berlin, Germany

关键词: TMA;    Renal cell carcinoma;    EMMPRIN;    RECK;   

Others  :  825102
DOI  :  10.1186/1479-5876-11-258

 received in 2013-05-30, accepted in 2013-10-03,  发布年份 2013

【 摘 要 】

Background

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.

Methods

Tumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray.

Results

RECK 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 r_s = 0.289 and r_s = 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.

Conclusions

We 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.

【 授权许可】

   
2013 Rabien et al.; licensee BioMed Central Ltd.

【 图 表 】

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