RGD Reference Report - Expression of p27 and its ubiquitin ligase subunit Skp2 in upper urinary tract transitional cell carcinoma. - Rat Genome Database

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Expression of p27 and its ubiquitin ligase subunit Skp2 in upper urinary tract transitional cell carcinoma.

Authors: Langner, C  Von Wasielewski, R  Ratschek, M  Rehak, P  Zigeuner, R 
Citation: Langner C, etal., Urology. 2004 Sep;64(3):611-6.
RGD ID: 2315044
Pubmed: PMID:15351619   (View Abstract at PubMed)
DOI: DOI:10.1016/j.urology.2004.04.072   (Journal Full-text)

OBJECTIVES: To analyze p27 and S-phase kinase-associated protein 2 (Skp2) expression in upper urinary tract transitional cell carcinoma (TCC) with respect to biologic significance. p27 (p27/kip1) is involved in cell cycle control, and loss of p27 protein expression may result in tumor development and/or progression. The association of p27 with the ubiquitin ligase subunit Skp2 targets p27 for degradation. METHODS: A total of 53 upper urinary tract TCC specimens were investigated immunohistochemically using a tissue microarray technique. The immunoreactivity of p27 and Skp2 was analyzed with respect to associations with pT stage, grade, and prognosis. RESULTS: Non-neoplastic renal tissue showed p27 immunoreactivity in tubule epithelium and pelvic urothelium, but lacked immunoreactivity for Skp2. In the TCC specimens, p27 immunoreactivity was noted in 47 (89%) of 53 cases. High p27 expression (50% or greater of tumor cell nuclei) tended to decrease with rising tumor stage (14 [45%] of 31 with pT1-pT2 versus 4 [18%] of 22 with pT3; P = 0.076), but was independent of tumor grade (11 [39%] of 28 grade 2 versus 7 [28%] of 25 grade 3-4; P = 0.56). Skp2 immunoreactivity was noted in 32 (60%) of 53 tumors. Skp2 expression increased with rising tumor stage (9 [41%] of 22 pT1 versus 23 [74%] of 31 pT2-pT3; P = 0.023) and tumor grade (12 [43%] of 28 grade 2 versus 20 [80%] of 25 grade 3; P = 0.043) and was associated with angioinvasion (P = 0.017). In multivariate analysis, tumor stage proved to be the only independent prognostic factor regarding disease-free survival. CONCLUSIONS: p27 and Skp2 are additional biomarkers in urogenital pathologic findings. The statistically significant association of Skp2 expression with high-grade TCC, as well as the lack of expression in non-neoplastic tissue, suggests that Skp2 could be a promising target for future cancer therapy strategies.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
SKP2Humantransitional cell carcinoma disease_progressionIEP protein:increased expression:kidneyRGD 
Skp2Mousetransitional cell carcinoma disease_progressionISORGD:1607086protein:increased expression:kidneyRGD 
Skp2Rattransitional cell carcinoma disease_progressionISORGD:1607086protein:increased expression:kidneyRGD 


Genes (Rattus norvegicus)
Skp2  (S-phase kinase associated protein 2)

Genes (Mus musculus)
Skp2  (S-phase kinase-associated protein 2)

Genes (Homo sapiens)
SKP2  (S-phase kinase associated protein 2)