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.

中文翻译：

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ATM蛋白与葡萄膜黑色素瘤的预后相关性及其与临床病理因素的关系。

目的葡萄膜黑色素瘤（UM）是一种眼内恶性肿瘤，通常由脉络膜引起，可导致视力丧失或转移。共济失调-毛细血管扩张突变（ATM）蛋白是DNA损伤反应的激活剂，其在葡萄膜黑色素瘤（UM）中的作用尚待探索。因此，本研究旨在检测ATM蛋白的表达和定位及其与临床病理参数的关系。方法：采用免疫组织化学方法对69份福尔马林固定石蜡包埋的脉络膜黑色素瘤样品进行核ATM（nATM）表达的研究，并通过Western印迹法进行验证。然后将结果与临床和组织病理学参数相关联。通过Kaplan-Meier分析和Cox危险比例法进行多元分析，确定预后的意义。结果在65％的病例中观察到nATM的丢失，在降低无病生存率方面具有统计学意义（p = 0.042）。在具有高风险组织病理学因素（例如上皮样细胞类型，肿瘤浸润性淋巴细胞和色素沉着可能有助于黑色素瘤进展）的病例中更常见这种损失。在多变量分析中，发现眼外扩散和nATM的丧失是独立的预后因素（p <0.05）。结论我们的数据表明，葡萄膜黑色素瘤发病机制中nATM蛋白的丢失可能是不良的预后标志物，可能导致转移的风险增加。肿瘤浸润淋巴细胞和高色素沉着可能有助于黑色素瘤的进展。在多变量分析中，发现眼外扩散和nATM的丧失是独立的预后因素（p <0.05）。结论我们的数据表明，葡萄膜黑色素瘤发病机理中nATM蛋白的丢失可能是不良的预后标志物，可能导致转移的风险增加。肿瘤浸润淋巴细胞和高色素沉着可能有助于黑色素瘤的进展。在多变量分析中，发现眼外扩散和nATM的丧失是独立的预后因素（p <0.05）。结论我们的数据表明，葡萄膜黑色素瘤发病机理中nATM蛋白的丢失可能是不良的预后标志物，可能导致转移的风险增加。