The Expression of Hypoxia-Inducible Factor 1α Is a Favorable Independent Prognostic Factor in Renal Cell Carcinoma

• Published in: Clinical cancer research Vol. 11; no. 3; pp. 1129 - 1135
• Main Authors: LIDGREN, Anders, HEDBERG, Ylva, GRANKVIST, Kjell, RASMUSON, Torgny, VASKO, Janos, LJUNGBERG, Börje
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-2005
• Subjects: Antineoplastic agents; Biological and medical sciences; HIF-1α; hypoxia-inducible factor; Kidneys; Medical sciences; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; prognosis; renal cell carcinoma; Tumors of the urinary system; Western blot; Kidney disease; Urinary system disease; Carcinoma; Prognosis; Grawitz tumor; Transcription factor HIF1; Malignant tumor; Gene expression
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.1129.11.3

Purpose: Renal cell carcinoma (RCC) is the most common malignancy of the kidney composed of specific tumor types. The sporadic conventional
RCCs are, in contrast to the other RCC types, characterized by a high rate of von Hippel-Lindau (VHL) mutations and hypermethylation.
The majority of these tumors lack functional VHL protein (pVHL) that leads to increased hypoxia-inducible factor 1α (HIF-1α)
expression. The pVHL is the physiologic regulator of the activity of HIF-1α by targeting it to the proteasome for degradation
under normoxia. Both pVHL and HIF-1α target other genes that are important for cancer survival and proliferation. Expression
of HIF-1α has been linked to poor prognosis in different malignancies, although few studies have been done on the relation
between HIF-1α and clinical variables in RCC.
Experimental Design: HIF-1α protein expression was analyzed in tumor tissue from 92 patients with RCC. HIF-1α was quantified by Western blot relative
to a positive control.
Results: The HIF-1α protein was expressed as two bands which strongly correlated ( r = 0.906, P < 0.001); therefore, they were added and the sum evaluated against clinicopathologic variables. There was no association
between HIF-1α and gender, stage, grade, tumor size, or vein invasion. Conventional RCCs had significantly higher HIF-1α expression
compared with papillary and chromophobe RCCs and kidney cortex. In conventional RCC, HIF-1α was an independent prognostic
factor.
Conclusion: HIF-1α levels varied significantly between the different RCC types. In conventional RCC, HIF-1α was an independent prognostic
factor. These data indicate that HIF-1α is involved in tumorogenesis and progression of RCC. Evaluation of other HIF target
gene products and correlation to angiogenesis seems warranted.