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European Urology

European Urology

Volume 50, issue 6, pages 1129-1386, December 2006

[Editorial Comments by V. Ficarra and by F. Keeley]

Hypoxia-Inducible Factor 1α Expression in Renal Cell Carcinoma Analyzed by Tissue Microarray

Anders Lidgren, Ylva Hedberg, Kjell Grankvist, Torgny Rasmuson, Anders Bergh and Börje Ljungberg

Accepted 30 May 2006, Published online 13 June 2006, pages 1272 - 1277


Abstract

Objectives

Angiogenesis is important for tumour progression and metastatic spread. Hypoxia-inducible factor 1α (HIF-1α) 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-1α expression using immunohistochemistry and related the results to RCC type and clinicopathologic variables.

Material and methods

We semiquantitatively analysed HIF-1α 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-1α staining was found mainly in the cytoplasm. The tumours were subdivided into HIF-1αLOW and HIF-1αHIGH on the basis of staining intensity. HIF-1α 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-1αHIGH-staining versus HIF-1αLOW-staining tumors. In conventional RCC there were significant differences in HIF-1α expression in relation to TNM stage, nuclear grade, and vein invasion. In patients with papillary RCC, difference in HIF-1α expression was observed only for nuclear grade.

Conclusions

We studied HIF-1α expression in RCC using tissue microarray. In patients with conventional RCC, HIF-1α levels were significantly lower in locally aggressive tumors versus localized tumors, and patients with high HIF-1α 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.

Keywords: Hypoxia-inducible factor, HIF-1α, RCC, Prognosis, Tissue microarray.


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