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染色质组装因子-1/p60 过表达有助于预测黑色素瘤患者的预后。

Overexpression of Chromatin Assembly Factor-1/p60 helps to predict the prognosis of melanoma patients.

机构信息

Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples Federico II, School of Medicine, Naples, Italy.

出版信息

BMC Cancer. 2010 Feb 24;10:63. doi: 10.1186/1471-2407-10-63.

Abstract

BACKGROUND

Cutaneous melanoma (CM) is the most lethal form of skin malignancy, which registers a constant increase in incidence worldwide. The identification of molecular alteration(s) involved in its biological aggressiveness represents a major challenge for researchers, considering that existing therapies are ineffective to treat metastasizing cases. The epigenetic control of chromatin dynamics during DNA synthesis, replication, and repair is fundamental for the orderly progression of cell proliferation. The Chromatin Assembly Factor 1 (CAF-1) complex acts as a major regulator of this process; its intermediate (p60) subunit has been recently proposed as a novel proliferation and prognostic marker for several tumors. We aimed to establish if the evaluation of the expression of CAF-1/p60 in primary CM may help define the prevision of outcome of patients.

METHODS

Immunohistochemistry with anti-CAF-1/p60 was performed on paraffin-embedded tissue sections of 130 cases of primary CM retrieved from the archive files of the Department of Biomorphological and Functional Sciences, Section of Pathology, University "Federico II" of Naples, Italy. Results were compared with histopathological and follow-up data of patients.

RESULTS

CAF-1/p60 was expressed in all CM. A significant statistical association between the overexpression of the protein and the occurrence of skin, node and/or distant metastases (P < 0.05) emerged, independently from histopathological prognostic factors.

CONCLUSIONS

CAF-1/p60 looks promising as a new prognostic marker for CM and sheds new light on the molecular events associated with photocancerogenesis and melanoma biology.The screening for CAF-1/p60 might contribute to the molecular sub-classification of CM, with improved translational outcomes.

摘要

背景

皮肤恶性黑素瘤(CM)是最致命的皮肤恶性肿瘤,其发病率在全球范围内呈持续上升趋势。鉴定参与其生物学侵袭性的分子改变对研究人员来说是一个重大挑战,因为现有的治疗方法对转移性病例无效。在 DNA 合成、复制和修复过程中,染色质动力学的表观遗传控制对细胞增殖的有序进行至关重要。染色质组装因子 1(CAF-1)复合物是该过程的主要调节剂;其中间(p60)亚基最近被提议作为几种肿瘤的新型增殖和预后标志物。我们旨在确定评估原发性 CM 中 CAF-1/p60 的表达是否有助于确定患者的预后。

方法

使用抗 CAF-1/p60 的免疫组织化学方法对来自意大利那不勒斯大学生物形态学和功能科学系病理学科档案文件的 130 例原发性 CM 石蜡包埋组织切片进行检测。将结果与患者的组织病理学和随访数据进行比较。

结果

CAF-1/p60 在所有 CM 中均有表达。该蛋白的过度表达与皮肤、淋巴结和/或远处转移的发生之间存在显著的统计学关联(P < 0.05),这与组织病理学预后因素无关。

结论

CAF-1/p60 有望成为 CM 的新预后标志物,并为光致癌发生和黑色素瘤生物学相关的分子事件提供新的见解。CAF-1/p60 的筛查可能有助于 CM 的分子亚分类,改善转化结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/2843674/1e4e39519406/1471-2407-10-63-1.jpg

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