Inhibitor of Apoptosis Proteins Gene Expression and Its Correlation with Prognostic Factors in Primary and Metastatic Uveal Melanoma

Abstract

Purpose: Members of the inhibitors of apoptosis proteins (IAPs) family are thought to promote tumor growth and interfere with response to therapy by suppressing apoptosis in several malignancies. We aimed to evaluate the expression of IAPs in uveal melanoma (UM) and its correlation with prognostic factors associated with death from metastatic UM. Methods: Expression of eight IAP genes [Baculoviral IAP repeat-containing (BIRC) 1–8] was evaluated through reverse transcription (RT)-PCR. BIRC5 and BIRC7 expression was measured using quantitative PCR (QPCR). BIRC5 protein expression was assessed with immunohistochemistry. QPCR results were correlated with apoptosis rate and with prognostic factors in UM, including lesion dimensions, cell type, monosomy 3, and vascular mimicry patterns. Results: IAP genes were expressed in the majority of primary and metastatic UM. BIRC5 and BIRC7 levels were 8.8-fold (p = 0.0003) and 7.0-fold (p = 0.003) higher in tumors (primary and metastatic tissue) vs. normal eye tissue, respectively. BIRC5 levels correlated with presence of monosomy 3 (p = 0.01) and higher levels of BIRC7 correlated with epithelioid cell type (p = 0.048). Conclusions: IAPs expression is up regulated in UM and is associated with some of its prognostic factors. Considering our findings together with previous reports on their role in a variety of malignancies and in UM cell lines, it is conceivable that IAPs contribute to the remarkable resistance of uveal melanoma to apoptosis-inducing chemotherapy.

KEYWORDS:

• BIRC5
• Birc7
• inhibitor of apoptosis proteins
• prognostic factors
• uveal melanoma