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Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors

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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.

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Acknowledgements

Jayanti Jha is thankful to the Indian Council of Medical Research for providing Research Assistant (RA). We are supported by Mr. Pankaj Kumar for providing technical support in IHC.

Funding

This work supported by the Indian Council of Medical Research (ICMR), New Delhi (ICMR File no: 5/13/17/2014-NCD-III).

Author information

Authors and Affiliations

  1. Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

    Jayanti Jha, Mithalesh Kumar Singh, Seema Sen & Seema Kashyap

  2. Department of Ophthalmology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

    Neelam Pushker & Mandeep Singh Bajaj

  3. Department of Biosciences, JMI, New Delhi, India

    Lata Singh

Authors
  1. Jayanti Jha
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  2. Mithalesh Kumar Singh
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  3. Lata Singh
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  4. Neelam Pushker
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  5. Mandeep Singh Bajaj
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  6. Seema Sen
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  7. Seema Kashyap
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Contributions

JJ executed the study, data analysis and in association with SK; MKS contributed to the design and draft of the manuscript. LS helped in the experiments and coordination of the manuscript. NP and MSB provide the enucleated specimens. SS and SK were responsible for histopathological examination. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Seema Kashyap.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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Jha, J., Singh, M.K., Singh, L. et al. Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors. Int J Clin Oncol 24, 1526–1535 (2019). https://doi.org/10.1007/s10147-019-01519-6

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  • DOI: https://doi.org/10.1007/s10147-019-01519-6

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