Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Department of Biosciences, JMI, New Delhi, India.
Int J Clin Oncol. 2019 Dec;24(12):1526-1535. doi: 10.1007/s10147-019-01519-6. Epub 2019 Aug 3.
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.
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).
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.
葡萄膜黑色素瘤（UM）是一种常见于脉络膜的眼内恶性肿瘤，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，但其在葡萄膜黑色素瘤（UM）中的作用尚未得到探索。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。
采用免疫组织化学法检测 69 例福尔马林固定石蜡包埋脉络膜黑色素瘤样本中核 ATM（nATM）的表达，并通过 Western blot 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 风险比例法的多变量分析来确定预后意义。
65%的病例观察到 nATM 缺失，与无疾病生存时间（p=0.042）显著相关。这种缺失在具有高危组织病理学因素（如上皮样细胞类型、肿瘤浸润淋巴细胞和高色素沉着）的病例中更为常见，这可能有助于黑色素瘤的进展。多变量分析显示，眼外扩散和 nATM 缺失是独立的预后因素（p<0.05）。
我们的数据表明，nATM 蛋白缺失可能是葡萄膜黑色素瘤发病机制中的一个不良预后标志物，可能导致转移风险增加。
