Hypoxic tumor microenvironment in advanced retinoblastoma.

Retinoblastoma (RB) is a malignant tumor of infancy and childhood. Unfavorable therapeutic response is still a quest in many tumors, including retinoblastoma. Hypoxic tumor microenvironment is one of the factors that determine the therapeutic response in many tumors. The purpose of this study was to determine the presence of hypoxia and its related proteins; Hypoxia inducible factor-1α (HIF-1α), Carbonic anhydrase IX (CA IX) and survivin in RB and their association with clinicopathological features. We evaluated the expression of HIF-1α and survivin by immunohistochemistry in 42 archival retinoblastoma tumors and CA IX; a hypoxia marker in 33 tumors in the same cohort. The expression was correlated with tumor groups based on invasion, differentiation and IIRC. Expression of HIF-1α, survivin and CA IX was observed in 83% (35/42), 86% (36/42), and 93% (31/33) of tumors respectively. We observed no significance between HIF-1α and CA IX expression in tumors with invasion, differentiation and in IIRC tumor groups. An increased survivin expression was observed in group E tumors than in group D tumors (P = 0.044). A significant association was observed between HIF-1α and survivin in differentiated (r = -0.582; P = < 0.01) and undifferentiated tumors groups (r = 0.513; P = <0.012). A similar significant association was observed between HIF-1α and CA IX in tumors with high immunoreactivity for HIF-1α (r = 0.833; P = <0.01). Based on these observations, we propose that HIF-1α pathway is deregulated in RB. The role of drug resistance and the potential of targeting HIF-1α, CA IX, and survivin in RB should further examined.