Journal of Clinical Oncology, Vol 15, 2570-2578, Copyright © 1997 by American Society of Clinical Oncology
Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma
Y Imazano, Y Takebayashi, K Nishiyama, S Akiba, K Miyadera, Y Yamada, S Akiyama and Y Ohi
Department of Cancer Chemotherapy, Institute for Cancer Research, Kagoshima University, Japan.
PURPOSE: Thymidine phosphorylase (TP) is identical to platelet-derived
endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We
examined whether TP expression in renal cell carcinoma (RCC) is associated
with microvessel density as a marker of angiogenesis, clinicopathologic
characteristics, and outcome. PATIENTS AND METHODS: The enzymatic activity
and expression of TP were examined in 18 RCCs and 19 kidney tissues not
grossly involved with tumor from 24 patients with 13 paired samples and 11
unpaired samples by spectrophotometry and immunoblotting. The relationship
between TP expression and microvessel density was assessed by
immunohistochemistry in 133 RCCs. RESULTS: The median enzymatic activity of
TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues
(P < .001). Similar results were obtained by immunoblot analysis.
According to the TP staining profile, tumors were classified as no or low,
intermediate, or high TP- expressing tumors. TP positivity was
significantly correlated with microvessel density. TP expression was
correlated with tumor grade, but there was no significant association
between TP expression and other clinicopathologic characteristics. TP
expression as a prognostic variable was studied using Cox's proportional
hazards model. TP overexpression was an independent prognostic factor
(hazards ratio, 3.95; 95% confidence interval, 0.98 to 15.89; P = .039) as
were nodal category, metastases category, tumor grade, and venous invasion.
CONCLUSION: These findings suggest that TP expression is correlated with
microvessel density in RCC and is an unfavorable independent prognostic
factor. The future development and characterization of TP inhibitors may
provide a novel approach to the therapy of RCC.
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