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染色质组装因子-1/p60 和多聚 [ADP-核糖] 聚合酶 1 在蕈样肉芽肿中的作用。

Role of chromatin assembly factor-1/p60 and poly [ADP-ribose] polymerase 1 in mycosis fungoides.

机构信息

Department of Advanced Biomedical Sciences, Pathology Section, School of Medicine, University of Naples "Federico II", Via Sergio Pansini, 5, 80131, Naples, Italy.

Haematopathology Unit, Department of Experimental Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

出版信息

Virchows Arch. 2021 May;478(5):961-968. doi: 10.1007/s00428-020-02952-z. Epub 2020 Oct 24.

DOI:10.1007/s00428-020-02952-z
PMID:33098490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8099834/
Abstract

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher's exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value < 0.05 was considered significant. PARP-1 was overexpressed in 57.9% of MF and was significantly associated with a MF stage > II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p < 0.001) but not with the MF stage (p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p < 0.001), although less strongly than CAF-1/p60 alone (χ = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.

摘要

蕈样肉芽肿(MF)是最常见的皮肤淋巴瘤类型。在大多数患者中,疾病呈缓慢进展和长期病程;然而,一部分患者表现出较差的肿瘤学结局。不幸的是,MF 没有可靠的预后标志物,并且目前可用的治疗方法仅对少数患者有效。本研究旨在评估 PARP-1 和 CAF-1/p60 在 MF 中的表达和临床意义。通过免疫组织化学评估 64 例 MF 代表疾病的不同阶段的 PARP-1 和 CAF-1/p60。使用 Fisher 确切检验和 Kaplan-Meier 生存分析与 Log-rank 检验评估 PARP-1 和 CAF-1/p60 与 MF 分期和结局的关联;p 值 < 0.05 被认为具有统计学意义。PARP-1 在 57.9%的 MF 中过表达,与 MF 分期 > II 显著相关(p = 0.034),但与死亡风险无关(p = 0.237)。CAF-1/p60 在 26.8%的 MF 中过表达,与总生存期缩短显著相关(p < 0.001),但与 MF 分期无关(p = 1)。PARP-1 过表达与 CAF-1/p60 过表达之间存在显著关联(p = 0.0025)。PARP-1 和 CAF-1/p60 同时过表达与总生存期缩短显著相关(p < 0.001),尽管与 CAF-1/p60 单独过表达相比相关性较弱(χ ² = 14.916 与 21.729,分别)。在 MF 中,PARP-1 在晚期阶段过表达,而 CAF-1/p60 在总生存期较短的病例中过表达,作为一个重要的预后标志物。可以合理地假设 PARP-1 抑制剂和抗 CAF-1/p60 靶向治疗在 MF 中可能具有作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/d47e23a53f40/428_2020_2952_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/c145ff167ffa/428_2020_2952_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/55b2503c3603/428_2020_2952_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/1d7dca7cbf68/428_2020_2952_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/d47e23a53f40/428_2020_2952_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/c145ff167ffa/428_2020_2952_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/55b2503c3603/428_2020_2952_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/1d7dca7cbf68/428_2020_2952_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/8099834/d47e23a53f40/428_2020_2952_Fig4_HTML.jpg

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