The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma
Article first published online: 16 FEB 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 7, pages 1336–1346, 1 April 2005
How to Cite
Shapira, M., Ben–Izhak, O., Linn, S., Futerman, B., Minkov, I. and Hershko, D. D. (2005), The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma. Cancer, 103: 1336–1346. doi: 10.1002/cncr.20917
- Issue published online: 18 MAR 2005
- Article first published online: 16 FEB 2005
- Manuscript Accepted: 2 DEC 2004
- Manuscript Revised: 11 NOV 2004
- Manuscript Received: 27 JUL 2004
- Israel Cancer Research Fund Clinical Research Career Development Award
- Israel Ministry of Health Award
- S-phase kinase-associated protein 2;
- cyclin kinase subunit 1;
- colorectal carcinoma
Loss of the cell-cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
MATERIALS AND METHODS
The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma.
Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression.
Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.