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.
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.
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.
a Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden
b Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
c Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden
d Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
Corresponding author. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, S-901 85 Umeå, Sweden. Tel. +46 90 785 1330; Fax: +46 90 125396.
© 2006 European Association of Urology, Published by Elsevier B.V.