p16INK4a expression and clinicopathologic parameters in renal cell carcinoma.
OBJECTIVE
The tumour suppressor gene p16INK4a is a cyclin-dependent kinase inhibitor, for which inactivation attributable to promoter hypermethylation or homozygous deletion has been described in malignancies. Little is known about p16INK4a protein levels in renal cell carcinoma (RCC) and its association with clinicopathologic parameters or disease progression.


METHODS
The expression of the p16INK4a gene was analysed with the use of immunohistochemistry and tissue microarrays (TMA). Tissue cores were obtained from the primary tumour itself, the tumoural invasion front, and histologically benign peritumoural tissue of 397 nephrectomies. For statistical analysis, sections were classified into four groups according to the relative amount of positively stained cells: negative (0%), low (1-10%), intermediate (11-50%), and high positivity (>50%). Follow-up data were analyzed for 198 patients (follow-up period: 2-240 mo; median: 138 mo).


RESULTS
Absent or low expression of p16INK4a was observed in 82% of tumour samples. No statistically significant association was found between protein levels detected in tumour, invasion front, or normal renal tissues and any of the clinicopathologic variables. Survival analysis by Kaplan-Meier revealed a significant association between high expression (>50%) of p16INK4a in tumours and better disease-specific survival (p=0.03, log-rank test). Cox regression analysis showed that p16INK4a expression is an independent covariate in disease-specific survival (p<0.01).


CONCLUSIONS
The absence of p16INK4a expression in most tumour cells indicates that p16INK4a could be involved in the tumourigenesis of RCC. Immunohistochemically detected positivity for p16INK4a is a positive prognosticator for specific survival in both uni- and multivariate analyses.
Ikuerowo
Stephen O
SO
Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany.
Kuczyk
Markus A
MA
von Wasielewski
Reinhard
R
Shittu
Olayiwola B
OB
Jonas
Udo
U
Machtens
Stefan
S
Serth
Jürgen
J
D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
D019941:Cyclin-Dependent Kinase Inhibitor p16