In situ analysis of Her2 DNA and RNA in retinoblastoma and adjacent retina.

• Type of Material: Article
• Authors: Gail M. Seigel, University at Buffalo; Dhaval K. Shah, University at Buffalo; Pia Mendoza, Emory Eye Center; Ezster Szalai, Emory Eye Center; Hans Grossniklaus, Emory University; Yinghui Song, Albert Einstein College of Medicine; Jidong Shan, Albert Einstein College of Medicine
• Language: English
• Date: 2019-07-23
• Publisher: Impact Journals LLC
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Seigel et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.18632/oncoscience.489
• Title of Journal or Parent Work: Oncoscience
• Volume: 6
• Issue: 7-8
• Start Page: 357
• End Page: 366
• Grant/Funding Information: This work was supported by the Childhood Eye Cancer Trust (GMS, DKS).
• Keywords: Adjacent tissues; Her2; Retinoblastoma
• Research Categories: Biology, Genetics; Health Sciences, Opthamology

Abstract

Retinoblastoma (RB) is an ocular tumor of early childhood. Current treatments attempt to preserve visual function, but may spare chemoresistant tumor cells. One potential therapeutic target for RB is HER2, (ERBB2), expressed in RB in truncated form. In this study, we tested the hypothesis that Her2 DNA and RNA are expressed in RB tumors and adjacent retina. We examined 24 human RB tumors as well as normal-appearing adjacent retinal tissues for Her2 DNA and RNA expression by in situ hybridization. We also examined 28 RB tumors for HER2 protein immunoreactivity. 21/22 RB tumors expressed Her2 DNA and 14/19 tumors expressed Her2 RNA. In 17 paired cases, there were three cases in which Her2 DNA was detected, but not RNA. We also saw Her2 RNA signal in six instances of "normal" adjacent retinal tissue. Heterogeneous HER2 protein expression in specific tumor regions also was confirmed by quantitative HER2 immunohistochemistry. In summary, Her2 DNA and RNA are expressed in many RB tumors, and in some adjacent ocular tissues, with hetereogenous protein expression throughout. These results may provide important insights regarding RB tumor progression, and drug targeting approaches designed to spare the eye, preserve vision and improve quality of life for RB patients.