News Releases

August 3, 2018
Media contact:  Leigh DeLozier, 404-778-3711, leigh.delozier@emory.edu

Hans E. Grossniklaus and his research team learn more about the best ways to follow and treat retinoblastoma

Emory Eye Center’s director of ocular oncology and pathology services, Hans E. Grossniklaus, MD, MBA, and others on his research team are working to learn whether genetic patterns can help indicate the best treatment for patients with retinoblastoma, or RB.

Retinoblastoma is the most common eye tumor in children, accounting for 6.1% of all cancers in children under age five. Advances in diagnosis and treatment over the last several decades have greatly improved the survival rate of these children but RB is still potentially lethal, especially in less-developed countries.

Depending on the level of risk involved and the stage of retinoblastoma at diagnosis, the affected eye might be saved by chemoreduction or chemotherapy.

“In order to determine whether a child who has his or her eye removed for RB needs chemotherapy, pathologists evaluate the tumor for high-risk features such as histologic findings of optic nerve invasion and choroidal invasion,” Grossniklaus explains. “However, over recent years, most eyes are not removed. Thus, there is the need for evaluation through a liquid biopsy of the aqueous of the eye.”

“Several years ago, our laboratory found that severe nuclear anaplasia (a finding in the nucleus of tumor cells) is as – or more – predictive of tumor spread than high-risk histologic features,” he adds.

Anaplasia in RB is usually categorized by three grades, or levels: mild, moderate, and severe. The team’s latest research showed that there are genetic changes in the DNA of severely anaplastic RB that are not present in mild or moderate anaplastic RB.

“This suggests that unique cellular processes drive the development of severe anaplasia rather than it being caused by further dysregulation of genes in mild or moderate anaplasia,” Grossniklaus says.

Other findings included:

  • Genes associated with nuclear proliferation are expressed differently in severe anaplasia

  • Photoreceptor gene expression is not present in severe anaplasia

  • Studying certain genes can accurately diagnose severe anaplasia

Numerous oncologic studies have indicated that gene-based analysis might prove more powerful and more easily applicable tools to predict a patient’s need for adjuvant therapy (such as chemotherapy). Gene-based tests are already in use for some ocular conditions such as uveal melanoma, but a comparable test for RB is not currently available. Research from Grossniklaus’ team helps demonstrate that creating a gene-based analysis for RB may be used as a clinical test.

“Our work identified a limited number of highly differentially expressed genes that were able to accurately predict all severe anaplasia samples in our dataset,” Grossniklaus says. “This establishes proof of the principle that particular genes could serve as surrogate markers of severe anaplasia and thus indicate high-risk retinoblastoma in a gene-based assay.”

“Further studies are needed to cross-validate the genes’ predictive ability,” he adds, “but these findings help pave the way for a liquid biopsy of aqueous fluid from children with RB to determine if the child needs chemotherapy. Our work, along with our collaborators, including Jesse Berry, MD, at the University of Southern California and J. William Harbour, MD, at the Bascom Palmer Eye Institute, will be used for liquid biopsies of retinoblastoma patients and help with their treatments.”

Their work has been published online in the American Journal of Pathology, with print publication to follow.

 

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