Abstract
Purpose :
EGFR (epidermal growth factor receptor, HER1) is a transmembrane growth factor receptor that is hyperactivated in variety of malignancies including breast, lung, brain, and colorectal cancers. EGFR overexpressing tumors can respond to FDA-approved monoclonal antibody therapies, such as cetuximab and panitumumab. In this study, we tested the hypothesis that EGFR is expressed in human retinoblastoma (RB), a childhood malignancy of the retina, with the potential to be targeted by anti-EGFR antibody based therapeutics.
Methods :
To test the hypothesis that EGFR is expressed in human retinoblastoma, we compared EGFR expression in four RB cell lines (Y79, WERI-RB27, RB143 and RB116) vs. three breast cancer cell lines (BT474, MCF7, and MDA-MB231), as well as RB tumor arrays (14 human RB cases) vs. breast cancer tumor arrays (48 human breast cancer cases) . We utilized immunocytochemistry and qRT-PCR methodologies to detect EGFR in our samples. For immunohistochemical analysis, we employed a commercial anti-EGFR antibody from Novus (Centennial, CO) along with three additional anti-EGFR antibodies (CPTC-EGFR-1, CPTC-EGFR-3 and CPTC-EGFR-5) developed by NCI and maintained at the Developmental Studies Hybridoma Bank. For qRT-PCR, we used primer pairs that were specific for all the transcript variants of EGFR and were not homologous to any other genes.
Results :
EGFR expression was established in a variety of RB cell lines and tumors by immunohistochemistry. Six of 14 RB tumors in a retinoblastoma tumor array exhibited 2+ or 3+ levels of immunoreactivity. Of the RB cell lines, RB116 showed the most intense EGFR immunoreactivity, with Y79 immunoreactive to a lesser degree. EGFR was also detected in Y79 and WERI-RB27 cells as well as in normal human retina by qRT-PCR.
Conclusions :
We have evaluated the expression of EGFR in human retinoblastoma tumors, cell lines and normal human retina. As with many biomarkers and drug targets, EGFR appears to be expressed to varying degrees in some RB tumors, but not all. These results provide important information as we develop novel EGFR-targeted antibody drug conjugates with a wider therapeutic index and fewer systemic side effects, designed to spare the eye and preserve vision in RB patients.
This is a 2020 ARVO Annual Meeting abstract.