p21 is a prognostic marker for renal cell carcinoma: implications for novel therapeutic approaches.
OBJECTIVE
Kidney cancer, although relatively rare compared to other malignancies, is the most lethal of the common urological malignancies. Current treatments are inadequate as evidenced by a poor 5-year survival of patients with metastatic disease. Since there exists a significant disparity in the survival of patients with localized vs metastatic disease, efforts are under way to identify molecular markers of progression as well as targets for novel therapeutic approaches. The apoptosis and cell cycle regulatory protein, p21(waf1/cip1), has been investigated as a possible target in other cancers since it is involved in the repair and apoptotic response of normal and malignant cells to DNA damage.


METHODS
We performed immunohistochemical analysis of a tissue array of 366 patients for which we have data on grade, stage and survival. We found that nuclear p21 is most highly expressed in collecting duct carcinoma and lowest in oncocytoma. Cytosolic p21 staining was highest in oncocytoma.


RESULTS
In clear cell renal cell carcinoma p21 has prognostic value, which is a function of whether patients have localized or metastatic disease at diagnosis, suggesting the existence of 2 discrete classes of this disease. In localized disease higher levels of nuclear p21 were associated with a better prognosis, but in patients with metastatic disease at diagnosis higher levels of nuclear and cytosolic p21 were associated with worse survival.


CONCLUSIONS
Based on our findings p21 may be useful in prognostication, and it may have a role in the differing biological behaviors of localized and metastatic renal cell carcinoma.
Weiss
Robert H
RH
Division of Nephrology, Department of Internal Medicine, University of California, Davis, California 95616, USA. rhweiss@ucdavis.edu
Borowsky
Alexander D
AD
Seligson
David
D
Lin
Pei-Yin
PY
Dillard-Telm
Lisa
L
Belldegrun
Arie S
AS
Figlin
Robert A
RA
Pantuck
Allan D
AD
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000378:metabolism; D011379:Prognosis
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21