Tenascin-C expression in retinoblastoma: A novel therapeutic target?

Abstract

Purpose : Retinoblastoma (RB) is the most common childhood intraocular tumor. The tenascin C (TN-C) has been associated with a considerable number of human cancers, being involved with increased cell migration, tissue remodelling and invasiveness of carcinomas. Recently, a study focused on the differential proteome of vitreous fluid in RB has highlighted the upregulation of TN-C (82.87 folds) in RB, as compared to controls. The aim of this study is to analyse the expression of TN-C in RB tissue and investigate the potential role as therapeutic target.

Methods : In total, 18 RB cases were evaluated from the MUHC-McGill University Ocular Pathology Laboratory. Immunohistochemistry was performed on paraffin-embedded tissue using monoclonal anti-TN-C antibodies. Slides were digitized using the Zeiss AxioScan.Z1 Scanner. Intensity of staining was evaluated using an Immunoreactive Score as mild (+1) or intense (+2); and further sub classified by the distribution of staining as focal or diffuse. An additional assessment of the optic nerve invasion was performed. Statistical analysis was performed using Fischer’s Exact Test; P<0.05 was considered significant.

Results : TN-C expression was positive in the normal uveal tract in 10 cases with focal distribution, the intensity score of 1 in 8 cases (80%) while a score of 2 was found in 2 cases (20%) where there was invasion of the optic nerve. In 5 cases, TN-C was positive in both uveal tract and tumor tissue with focal distribution in all the cases; an intensity score of 1 in 4 cases (80%), and 1 case with an intensity score of 2 with an optic nerve invasion. In 2 cases, the expression of TN-C was found isolated within the tumor with a focal distribution and intensity of 1 in both cases. Six cases out of 18 RB featured invasion of the optic nerve. In 3 out of 7 cases where the TN-C was positive within the tumour there was invasion of the optic nerve (p>0.05).

Conclusions : To the best of our knowledge, this is the first study to analyse the expression of TN-C in RB tissue. The RB tissue examined was seldom positive for TN-C expression. These results may correlate with studies where the TN-C was found upregulated in vitreous of RB patients. The fact that TN-C was positive in normal ocular tissues in RB cases with optic nerve invasion may indicate overexpression of TN-C in more malignant disease. Further studies are needed to clarify the potential role of TN-C in target therapies in RB.

This is a 2020 ARVO Annual Meeting abstract.