‘C-myc Oncogene Expression as a prognostic marker in Uveal Melanoma’ Dr. Aaron Donnelly

Annual Grant Scheme 2020

Uveal Melanoma (UM) is the most common intraocular malignancy in adults with an annual incidence in Ireland estimated at 9.5 cases per million people.1 Almost 50% of patients with UM will develop metastases, the average survival after detection of metastases being only 10 months. 2, 3

Detecting those patients who are at increased risk of developing metastases is important for clinical management, as metastases are not usually detectable at the time of treatment of the primary tumour and have often reached an advanced stage by the time they cause symptoms. 4 The ability to stratify patients into high risk or low risk for metastases based on the cytogenetic profile of their tumour will allow us to reassure those patients who are at low risk of metastatic disease. Conversely, those at high risk can undergo more regular surveillance and might also be considered for adjuvant therapies.

A clinical study of prophylactic chemotherapy would also be desirable; however, regarding the side-effects of chemotherapy, identification of a high-risk group is regarded as a prerequisite for such a study. 5

Although several clinical and histopathologic parameters serve as established prognostic factors in UM, none of them have been regarded as sufficient for a clear definition of clinically relevant subgroups of patients. The understanding of the role which various genetic anomalies play in UM tumorigenesis may finally lead to risk-adjusted therapy strategies.

C-myc is one such marker that could act as a prognostic indicator in UM. C-Myc is a nuclear oncogene involved in cellular proliferation, and its expression is linked with the ability of cells to proceed through the cell cycle. 6 Aberrant expression of C-myc has been related to the deregulation of proliferation in several tumor types.7

Overexpression of the C-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in uveal melanoma genesis. 8-10 The gene for C-Myc is located on chromosome 8q24.1 and chromosomal abnormalities involving amplification of 8q material have been associated with poor prognosis in uveal melanoma also. 11-13

To date, only a limited number of studies have examined the role of C-myc in uveal melanoma.7, 14-18 The results from these studies have varied with one paper demonstrating improved survival15 and another, decreased survival17 with increasing levels of C-myc expression.

The aim of our study is to assess C-myc positivity in uveal melanoma samples obtained at RVEEH between 2010 and 2020. We will determine any significant association between C-myc positivity and survival. We would also determine the association between C-myc positivity and a number of putative clinicopathological tumour characteristics.

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