HER2 Overexpression in Retinoblastoma: A Potential Therapeutic Target

Abstract

Background: Retinoblastoma (RB) is the most common primary intraocular malignancy. Current therapies are associated with high morbidity in the short- and long-term. Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein detected in 15-30% of breast cancers, but it has also been described in other malignancies. Recently, it has been claimed that a truncated version of this protein is expressed in RB, responsive to directed therapies in vitro. We scored HER2 overexpression in RB tissue samples and discussed its potential clinical utility. Methods: HER2 overexpression was investigated using immunohistochemistry; the overexpression was evaluated with a score ranging from 0 to 3+ according to the membranous staining pattern in archival formalin-fixed, paraffin-embedded RBs. Results: A total of 60 RB cases and a RB cell line (Y79) were considered. The mean age at enucleation was 31.6 ± 31.5 months. The mean time from diagnosis to enucleation was 11.8 ± 11.2 months (range 1-44). Five (8%) cases were multifocal. HER2 overexpression was negative in all RB cases (49 cases scored 0 and 11 scored 1+) and in the Y79 cell line. Conclusions: Overall, we were not able to demonstrate the overexpression of HER2. Further studies should clarify and better elucidate the potential role of HER2-targeted therapies in RB.

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

“…This study focused on the tumor itself, without analysis of adjacent retinal tissues. A subsequent study by Sousa and colleagues questioned the extent of HER2 expression in retinoblastoma, as the protein was immunonegative in 49/60 retinoblastoma cases and very low in 11/60 cases that they tested [9]. Since the Sousa study involved one of the same antibodies used in our study (Sigma, HPA001383), the simplest explanation for this conflicting result was a difference in methodology (shorter incubation periods, different detection methods).…”