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Hypoxia-inducible factor 1alpha expression in renal cell carcinoma analyzed by tissue microarray.

Lidgren A, Hedberg Y, Grankvist K, Rasmuson T, Bergh A, Ljungberg B

Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.

OBJECTIVES: Angiogenesis is important for tumour progression and metastatic spread. Hypoxia-inducible factor 1alpha (HIF-1alpha) 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-1alpha expression using immunohistochemistry and related the results to RCC type and clinicopathologic variables. MATERIAL AND METHODS: We semiquantitatively analysed HIF-1alpha 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-1alpha staining was found mainly in the cytoplasm. The tumours were subdivided into HIF-1alpha(LOW) and HIF-1alpha(HIGH) on the basis of staining intensity. HIF-1alpha 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-1alpha(HIGH)-staining versus HIF-1alpha(LOW)-staining tumors. In conventional RCC there were significant differences in HIF-1alpha expression in relation to TNM stage, nuclear grade, and vein invasion. In patients with papillary RCC, difference in HIF-1alpha expression was observed only for nuclear grade. CONCLUSIONS: We studied HIF-1alpha expression in RCC using tissue microarray. In patients with conventional RCC, HIF-1alpha levels were significantly lower in locally aggressive tumors versus localized tumors, and patients with high HIF-1alpha levels tended to have a better prognosis. There seems to be a diverging regulation of angiogenesis between the different RCC types. Further studies of HIF and angiogenesis in RCC are encouraged.

Published 13 November 2006 in Eur Urol, 50(6): 1272-7.
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