Hypoxia-inducible factor lot expression in renal cell carcinoma analyzed by tissue microarray

Objectives: Angiogenesis is important for tumour progression and metastatic spread. Hypoxia-inducible factor la (HIF-1 alpha) is a major factor regulating a number of other angiogenic factors. Renal cell carcinoma (RCC) is a malignancy with a variable clinical course, partly attributable to specific genetic alterations of the different RCC types. We therefore analysed HIF-1 alpha expression using immunohistochernistry and related the results to RCC type and clinicopathologic variables. Material and methods: We semiquantitatively analysed HIF-1 alpha expression using immunohistological staining of a prepared tissue microarray. There were 216 patients including 176 conventional, 26 papillary, and 14 chromophobe RCCs. Results: The HIF-1 alpha staining was found mainly in the cytoplasm. The tumours were subdivided into HIF-1 alpha(LOW) and HIF-1 alpha(HIGH) on the basis of staining intensity. HIF-1 alpha expression between the RCC types did not differ. Patients with conventional RCC showed a trend (p = 0.055) towards a prolonged survival for those with HIF-1 alpha(HIGH)-staining versus HIF-1 alpha(LOW)-staining tumors. In conventional RCC there were significant differences in HIF-1 alpha expression in relation to TNM stage, nuclear grade, and vein invasion. In patients with papillary RCC, difference in HIF-1 alpha. expression was observed only for nuclear grade. Conclusions: We studied HIF-1 alpha expression in RCC using tissue microarray. In patients with conventional RCC, HIF-1 alpha levels were significantly lower in locally aggressive tumors versus localized tumors, and patients with high HIF-1 alpha levels tended to have a better prognosis. There seems to be a diverging regulation of angiogenesis between the different RCC types. Further studies of HIT and angiogenesis in RCC are encouraged. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.