The role of nitric oxide synthases and nitrotyrosine in retinoblastoma

Abstract

To investigate the potential involvement of the nitric oxide (NO) pathway in retinoblastoma, the authors correlated immunoreactivity for endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine (NT) with the degree of tumor invasiveness in retinoblastoma. eNOS, iNOS, and NT reactivity was evaluated by immunohistochemistry in 34 archival retinoblastoma specimens and in a human Y79 retinoblastoma cell line. The tumors were divided into 2 groups: Group A tumors (n = 17 tumors) with no invasion and Group B tumors (n = 17 tumors) with invasion of the choroid, optic nerve, and/or orbit. The expression levels of eNOS, iNOS, and NT were correlated with invasiveness of the tumors. In Group A tumors (n = 17 tumors) without invasion, eNOS was positive in 17 of 17 tumors (100%), iNOS was positive in 14 of 17 tumors (82%), and NT was positive in 17 of 17 tumors (100%). In Group B tumors (n = 17 tumors) with invasion, eNOS was positive in 17 of 17 tumors (100%), iNOS was positive in 16 of 17 tumors (94%), and NT was positive in 17 of 17 tumors (100%). The invasive cohort showed significantly higher expression of iNOS (P < 0.0001) and NT (P < 0.020) compared with the noninvasive cohort. Y79 cells also expressed eNOS, iNOS, and NT; and nonneoplastic retina was positive for eNOS, iNOS, and NT. Taken together, the results suggested that retinoblastomas can produce NO. The roles of NO in the biology of retinoblastoma and in the prognosis for patients with retinoblastoma remain to be established.