Relationship between HIF-1 ALPHA, HIF-2 ALPHA and HAF expression profile and prognostic parameters in renal cell carcinoma

Kidney cancer is the 14th most frequent type of cancer among males and 9th in females according to World Health Organization (WHO) researchs. The 16th most common cause of cancer worldwide is death. Tumor cells and tumor metastases are exposed to low oxygen levels / hypoxia. In hypoxia response, there are two important mediators, HIF-1α and HIF-2α. HIFs are the most important regulators of cellular stress and members of the tyrosine kinase pathway. Hypoxia associated factor (HAF); has a role conversion of HIF-1 α to HIF-2 α. HAF is responsible for evolution of tumor stem cells and aggressive behavior of the tumor. HIF-1α, HIF-2α and HAF levels associated with poor survival time, tumor aggressiveness, tumor size and invasion. In this study, 239 patients diagnosed with renal cell carcinoma between 2006-2014 in Ankara Yıldırım Beyazıt University / Ankara Atatürk Training and Research Hospital Department of Pathology were subjected to immunohistochemistry of HIF-1α, HIF-2α and HAF antibodies by TMA blocks. In this study HIF-1α cytoplasmic expression was correlated with pelvicalyceal system infiltration and histological subtype. There was a significant correlation between HIF-1α nuclear expression and histological type and ISUP nuclear grade. Relationship between HAF and histological type and ISUP nuclear grade was observed. HIF-2α expression was correlated with histological subtype, tumor size, renal sinus infiltration and adrenal gland metastasis. No association was found between HIF-1α, HIF-2 α and HAF expression levels in other clinicopathological features of the cases. In our study, HAF expression increased with decreasing HIF-1α nuclear expression in accordance with the literature, and a statistically significant negative correlation was detected between these two. In addition, as the expression of HAF increased, the expression of HIF-2α was also increased and the relationship between them was statistically significant. There are publications in which HIF-1α nuclear, HIF-2α and HAF expression are associated with poor prognosis and HIF-1α cytoplasmic expression is associated with good prognosis in renal cell carcinoma patients. However, number of studies which subjected on tumor tissues and case numbers are limited.