Expression of hypoxia-inducible factors in clear-cell renal cell carcinoma tumors of adults with and without obstructive sleep apnea

Abstract

INTRODUCTION: Upregulation of hypoxia-inducible factors (HIF) is an important pathologic feature shared by clear-cell renal cell carcinoma (ccRCC) and obstructive sleep apnea (OSA). It is unclear whether OSA alters ccRCC pathogenesis via HIF expression. This study aimed to characterize differences in HIF expression in ccRCC tumors in patients with and without OSA. We hypothesized that a diagnosis of OSA was associated with increased HIF expression.

METHODS: A cohort of adults who underwent nephrectomy for ccRCC was identified. OSA diagnosis was determined with preoperative STOP-BANG scores or polysomnography, selecting 20 individuals with and 20 without OSA. Tumor sections were immunohistochemically stained for HIF-1α & HIF-2α and assessed by an expert uropathologist.

RESULTS: The OSA group exhibited a higher prevalence of hypertension (95% vs. 50%, p=0.001) and greater median body mass index (BMI) (34.8 vs. 29.05, p=0.006). Tumor grades were higher in the OSA group (p=0.039). No differences were noted in tumor stages. Samples of ccRCC tumors in the OSA group demonstrated a higher prevalence of HIF-1α positivity (80% vs. 50%, p=0.048), although median histoscores were not different (4 vs. 2.5, p=0.260). Neither median HIF-2α histoscores (1 vs. 2, p=0.306) nor expression (histoscore >0; 74% vs. 75%, p=0.927) was statistically significant.

CONCLUSIONS: In OSA patients, ccRCC tumors exhibited higher HIF-1α positivity and tumor grades; however, no significant differences in median HIF histoscores, HIF-2α expression, or tumor stage were found. Future studies can use our results to perform formal sample size calculations and elucidate the role of OSA in the pathogenesis of ccRCC.