Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas
Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas
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DOI：
10.1111/jop.12453
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发表时间：
2016-11-01
影响因子：
3.3
通讯作者：
Modolo, Filipe
中科院分区：
文献类型：
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作者：
Daniel, Filipe I.;Alves, Soraia R.;Modolo, Filipe
背景技术背景：表观遗传修饰，包括由DNA甲基转移酶（DNMT）进行的肿瘤抑制基因的DNA甲基化，是癌症发生中的重要事件。虽然有关于其在几种癌症类型中的表达的研究，但DNMTs在光诱导的唇癌发生中的表达模式尚不清楚。本研究旨在探讨DNMTs 1、3a和3b在唇癌前病变中的表达方法：选取30例光化性唇炎（AC）、30例唇鳞癌（LSCC）和20例非肿瘤组织（NNT），进行DNMTs 1、3a和3b的免疫组化研究。DNMT 1阳性率在喉鳞癌组（68.6%）明显高于正常喉黏膜（47%），DNMT 3b阳性率在喉鳞癌组（70.9%）明显高于正常喉黏膜（37.9%）和腺癌（44%）。只有DNMT 3a在AC细胞核和胞浆中均有较高的表达（分别为35.9%和35.5%）（分别为4.4%和16.1%）和LSCC（分别为8.8%和13.2%）（P < 0.05）。结论：结果表明，DNMT 3a可能在AC中存在的UV致癌的初始步骤的甲基化过程中起关键作用，而DNMT 3b可能负责UV致癌的初始步骤的甲基化过程。在已经确定的唇癌中进行从头甲基化。
BACKGROUND: Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer.METHODS: Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b.RESULTS: Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05).CONCLUSIONS: The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer.