title: Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?
abstract: OBJECTIVE
  To evaluate retrospectively kidney-specific cadherin (Ksp-cad) expression in renal cell carcinoma (RCC) subtypes and oncocytoma in correlation with its ontogenetic origin of distal and proximal tubules and to correlate Ksp-cad expression with tumour characteristics.
  
  
  METHODS
  Membranous and cytoplasmic expression of Ksp-cad was determined in 40 clear cell (ccRCC), 25 papillary (pRCC), 19 chromophobe carcinomas (chRCC), 27 oncocytomas (oncocytomas) (n = 111) and 32 benign kidney parenchyma specimens separated in distal tubules (DT) and proximal tubules (PT) by immunohistochemistry using tissue microarray technique. Staining intensity was quantified as a score ranging from 0 to 12. Comparison of data and correlation with tumour characteristics were done by Wilcoxon/Kruskal-Wallis tests (post hoc Tukey-Kramer analysis).
  
  
  RESULTS
  In benign renal tissue, membranous and cytoplasmic expression of Ksp-cad in the DT was significantly higher than that in the PT (12.0 ± 0 vs. 5.2 ± 0.3 and 6.3 ± 0.5 vs. 0.0 ± 0.0, respectively; (P < 0.05)). Membranous KSP-cad expression was significantly higher in chRCC (5.2 ± 0.8) and oncocytomas (3.7 ± 0.4) than that in ccRCC (0.8 ± 0.2) and pRCC (1.4 ± 0.4; P < 0.05), while expression between oncocytomas and chRCC did not differ significantly. In RCC, Ksp-cad expression was significantly associated with higher T stage and the occurrence of synchronous metastasis (P < 0.05). Higher N stages and grading tended to correlate with a lower Ksp-cad expression.
  
  
  CONCLUSIONS
  In this cohort, the origin of tumour subtypes-chRCC and oncocytomas develop from DT and ccRCC and pRCC from PT cells-is mirrored by the respective Ksp-cad expression. This raises the question whether DT-derived tumours have a less malignant potential than PT-derived tumours.
authors.affiliation: Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Strasse 3, Tuebingen, Germany. marcushorstmann@gmx.ch
authors.forename: M
authors.initials: M
authors.lastname: Horstmann
authors.forename: L M
authors.initials: LM
authors.lastname: Geiger
authors.forename: U
authors.initials: U
authors.lastname: Vogel
authors.forename: H
authors.initials: H
authors.lastname: Schmid
authors.forename: J
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: U
authors.initials: U
authors.lastname: Kuehs
authors.forename: A S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: S
authors.initials: S
authors.lastname: Kruck
authors.forename: A
authors.initials: A
authors.lastname: Stenzl
authors.forename: J
authors.initials: J
authors.lastname: Bedke
mesh_terms: D018249:Adenoma, Oxyphilic / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D019070:Cell Lineage; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D007686:Kidney Tubules, Distal / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C087310:K cadherin