Daniel Filipe I, Alves Soraia R, Vieira Daniella S C, Biz Michelle T, Daniel Inah W B S, Modolo Filipe
Pathology Department and Dentistry Graduate Program, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil.
Private Dentist, Florianopolis, Santa Catarina, Brazil.
J Oral Pathol Med. 2016 Nov;45(10):774-779. doi: 10.1111/jop.12453. Epub 2016 May 9.
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.
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.
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).
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.
表观遗传修饰，包括由DNA甲基转移酶（DNMTs）进行的肿瘤抑制基因的DNA甲基化，是致癌过程中的重要事件。尽管有研究涉及其在几种癌症类型中的表达，但在光诱导性唇癌发生过程中DNMTs的表达模式尚不清楚。本研究的目的是调查DNMTs 1、3a和3b在唇部癌前病变（光化性唇炎）和癌症中的免疫表达情况。
选取30例光化性唇炎（AC）、30例唇鳞状细胞癌（LSCC）和20例非肿瘤组织（NNT），对DNMTs 1、3a和3b进行免疫组织化学研究。
与NNT组（47%）相比，LSCC组核DNMT 1免疫反应性显著更高（68.6%），且LSCC组核DNMT 3b（70.9%）高于NNT组（37.9%）和AC组（44%）。仅DNMT 3a在AC组中的核表达和胞质表达均高于NNT组（分别为35.9%和35.5%）和LSCC组（分别为8.8%和13.2%）（P < 0.05）。
结果表明，DNMT 3a可能在AC中存在的紫外线致癌初始步骤的甲基化过程中起关键作用，而DNMT 3b可能负责已形成的唇癌中的从头甲基化。
