Uveal melanoma (UM) is an intraocular malignancy commonly arising from choroid which can cause visual loss or metastasis. Till date, there is no current study available on UM with respect to ATM (Ataxia Telangiectasia Mutated) protein that induces DNA damage response. Several studies revealed that loss of nuclear ATM (nATM) in various cancers like pancreatic, colorectal, gastric cancer leads to poor prognosis. This signifies ATM protein as a prognostic biomarker for cancer progression. Therefore, the aim of the study is to detect the expression/localization of ATM protein in uveal melanoma patients.
Expression of nATM was investigated on 69 formalin fixed paraffin embedded choroidal melanoma samples by immunohistochemistry and validated by western blotting. Results were then correlated with clinical and histopathological parameters. To determine the prognostic significance, Kaplan–Meier analysis and multivariate analysis by Cox’s Proportional Hazards Model was performed.
There was a male preponderance in our study. Histopathological high-risk factors were identified in 30/69 (43.5%) cases. Loss of nATM was found in 65.2% of the cases. Loss of nATM was statistically significant with epithelioid cell type, high pigmentation, LTD >10mm, HRFs>1, tumour height and advanced tumour staging (p < 0.05). On multivariate analysis, advanced tumour staging found out to be an independent prognostic factor.
Our data suggest that loss of nATM protein might serve as a potential prognostic marker in the pathogenesis of uveal melanoma and leads to increased risk of metastasis. These findings demonstrate an important role of ATM protein and may have a therapeutic potential in uveal melanoma. However, further studies are required in a larger cohort of patients with longer follow up and translational validation needs to be performed.
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All authors have declared no conflicts of interest.