Clinicopathologic significances of nuclear expression of nuclear factor-κB transcription factors in retinoblastoma

AIMS: The nuclear factor-κB (NF-κB) transcription factors family is thought to play an important role in the development of certain cancers. In this study, the clinical significance of NF-κB transcription factor expression and the MIB-1 labelling index (MIB-1 LI) were studied in retinoblastoma. METHODS: Immunohistochemical analysis of normal retina (n=6) and retinoblastoma tumour (n=62) specimens obtained from multiple centres was performed in order to evaluate the pathological associations of NF-κB subunits and retinoblastoma. RESULTS: Expression of NF-κB proteins was frequently detected in retinoblastoma but not in normal retina samples with c-Rel being the most commonly detected (61%). This protein was more frequently detected in poorly-differentiated and invasive tumours than in well-differentiated and non-invasive tumours. RelA expression in invasive tumours was also significantly higher. Furthermore, expression of c-Rel correlated positively with the MIB-1 LI in retinoblastoma, and RelA/c-Rel revealed positive correlation with RelA/RelB. CONCLUSIONS: This study demonstrated that expression of RelA and c-Rel proteins represents a reliable prognostic marker of retinoblastoma and that NF-κB is related to retinoblastoma tumorigenesis and progression through a non-conventional pathway. This data suggests that therapeutic strategies targeting NF-κB combined with other therapies may represent a novel approach to retinoblastoma therapy.