title: Biological significance of p27 and Skp2 expression in renal cell carcinoma. A systematic analysis of primary and metastatic tumour tissues using a tissue microarray technique.
abstract: p27 (p27/kip1) is involved in cell-cycle control, and loss of p27 expression may result in tumour development and/or progression. Association with Skp2 targets p27 for degradation. Using a tissue microarray technique, 171 primary renal cell carcinomas (RCCs) and 58 RCC metastases were immunostained for p27 and Skp2. p27 Immunoreactivity was noted in 83 of 129 (64%) clear cell, 6 of 22 (27%) chromophobe and 15 of 20 (75%) papillary tumours as well as 44 of 58 (76%) metastases. In clear cell cancers, high p27 expression (> or =50% of tumour cells) decreased with rising tumour stage (50% pT1/pT2 versus 20% pT3; P<0.001) and grade (44% G1/G2 versus 21% G3/G4; P=0.008). None of 22 chromophobe cancers showed high expression in contrast to 46 of 129 (36%) clear cell tumours (P<0.001). Skp2 expression was noted in 8 of 129 (6%) clear cell cancers and 11 of 55 (20%) metastases (P=0.008). Immunoreactivity increased with rising tumour stage (1% pT1/pT2 versus 11% pT3; P=0.03) and grade (1% G1/G2 versus 15% G3/G4; P=0.004) and was associated with sarcomatoid morphology (P<0.001). In multivariate analysis, patients with low p27 expression and Skp2 immunoreactivity in clear cell cancers had a less favourable outcome. In conclusion, p27 and Skp2 proved to be additional biomarkers in renal cancer pathology with both prognostic and diagnostic impact.
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. cord.langner@meduni-graz.at
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.forename: Reinhard
authors.initials: R
authors.lastname: von Wasielewski
authors.forename: Manfred
authors.initials: M
authors.lastname: Ratschek
authors.forename: Peter
authors.initials: P
authors.lastname: Rehak
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D018797:Cell Cycle Proteins / Q000032:analysis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis*; D046888:Tissue Array Analysis / Q000379:methods*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D018797:Cell Cycle Proteins; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27