title: Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.
abstract: 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 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.
  
  
  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.
authors.affiliation: Department of Urology, Research Division, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany. anja.rabien@charite.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Rabien
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
mesh_terms: D051926:Basigin / Q000378:metabolism*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: C497886:BSG protein, human; D058851:GPI-Linked Proteins; C115460:RECK protein, human; D051926:Basigin