Jayanti Jha1, Mithalesh Kumar Singh1, Lata Singh2, Neelam Pushker3, Mandeep Singh Bajaj3, Seema Sen1, Seema Kashyap4. 1. Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 2. Department of Biosciences, JMI, New Delhi, India. 3. Department of Ophthalmology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 4. Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. dr_skashyap@hotmail.com.
Abstract
PURPOSE: Uveal melanoma (UM) is an intraocular malignancy commonly arising from choroid which can cause visual loss or metastasis. Ataxia-telangiectasia mutated (ATM) protein is an activator of DNA damage response and its role in uveal melanoma (UM) is still unexplored. Therefore, the study aims to detect the expression and localization of ATM protein and its association with clinicopathological parameters METHODS: Expression of nuclear ATM (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. Prognostic significance was determined by the Kaplan-Meier analysis and the multivariate analysis by Cox's hazard proportional method. RESULTS: Loss of nATM was observed in 65% of cases, which was statistically significant with the reduced disease-free survival (p = 0.042). This loss was more frequently found in cases with high-risk histopathological factors like epithelioid cell type, tumor infiltrating lymphocytes and high pigmentation which might help in the progression of melanoma. On multivariate analysis, extraocular spread and loss of nATM were found to be independent prognostic factors (p < 0.05). CONCLUSION: Our data suggest that loss of nATM protein might serve as a poor prognostic marker in the pathogenesis of uveal melanoma which may lead to increased risk of metastasis.
PURPOSE:Uveal melanoma (UM) is an intraocular malignancy commonly arising from choroid which can cause visual loss or metastasis. Ataxia-telangiectasia mutated (ATM) protein is an activator of DNA damage response and its role in uveal melanoma (UM) is still unexplored. Therefore, the study aims to detect the expression and localization of ATM protein and its association with clinicopathological parameters METHODS: Expression of nuclear ATM (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. Prognostic significance was determined by the Kaplan-Meier analysis and the multivariate analysis by Cox's hazard proportional method. RESULTS: Loss of nATM was observed in 65% of cases, which was statistically significant with the reduced disease-free survival (p = 0.042). This loss was more frequently found in cases with high-risk histopathological factors like epithelioid cell type, tumor infiltrating lymphocytes and high pigmentation which might help in the progression of melanoma. On multivariate analysis, extraocular spread and loss of nATM were found to be independent prognostic factors (p < 0.05). CONCLUSION: Our data suggest that loss of nATM protein might serve as a poor prognostic marker in the pathogenesis of uveal melanoma which may lead to increased risk of metastasis.
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