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R. J. Barry, L. R. M. Santos, J.-C. Marshall, M. E. Orellana, C. Martins, M. N. Burnier, Jr.; Expression of C-kit in Retinoblastoma: A Potential Therapeutic Target. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1605. doi: https://doi.org/.
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Despite success in the treatment of primary retinoblastoma, there is a significant incidence of recurrence, metastatic disease and subsequent death in affected individuals. This observation along with the occurrence of multidrug resistance has fostered the development of a new class of cytotoxic agents targeting individual genes with altered expression in tumor cells. C-kit is a 145 kDa transmembrane tyrosine kinase protein thought to play an important role in tumorigenesis. With the development of the compound Imatinib Mesylate (STI571, Gleevec®, Novartis Pharma AG Basel, Switzerland) which specifically inhibits tyrosine kinase receptors, C-kit has emerged as a potential therapeutic target. This study aims to determine the immunoexpression of C-kit in retinoblastoma enucleated globes and correlate this expression with histopathological prognostic features.
Eighty-four paraffin-embedded enucleation globes of retinoblastoma were collected from the archives of the Henry C. Witelson Ocular Pathology Registry. C-kit immunohistochemistry was performed using the Ventana BenchMark fully automated machine. The C-kit staining was used according to the protocol provided by Ventana Medical System Inc. Arizona, and two experienced ocular pathologists analyzed all slides. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve. Odds ratios were calculated to quantify differences in C-kit expression between tumours with different patterns of invasion.
Twenty-one (25%) slides were excluded from analysis due to the presence of extensive tissue necrosis or absence of sufficient optic nerve segment for analysis. C-kit expression was identified in 33/63 (53.8%) sections analyzed. 31/50 tumors (62%) with extra-retinal invasion displayed immunohistochemical expression of C-kit, compared with only 2/13 tumours (15.4%) with no invasion beyond the retina (OR: 8.97, 95% confidence interval: 1.79 - 44.95). Overall, 28/44 specimens with choroidal involvement (59.9%), and 20/29 with optic nerve involvement (68.96%) expressed immunoreactivity for C-kit.
More than half of Retinoblastomas in this study expressed C-kit. The expression of C-kit in these retinoblastomas strongly correlated with histopathological features of worse prognosis including optic nerve and choroidal invasion. This study supports further investigation for possible use of Imatinib Mesylate for adjuvant treatment of aggressive retinoblastomas.
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