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口腔扁平苔藓与恶性转化:p16、Ki-67、Bub-3和SOX4在评估癌前潜能中的作用。

Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential.

作者信息

Rosa Eduardo Augusto, Hurtado-Puerto Aura Maria, Falcão Denise Pinheiro, Brietzke Aline Patricia, De Almeida Prado Franceschi Luiz Eduardo, Cavalcanti Neto Florlorêncio Figueiredo, Tiziane Valdenize, Carneiro Fabiana Pirani, Kogawa Evelyn Mikaela, Moreno Heitor, Amorim Rivadávio Fernandes Batista

机构信息

Post-Graduation Program in Medical Sciences, Department of Pathology, School of Medicine, University of Brasília, Brasília 70910-900, Brazil.

Laboratory for Neuropsychiatry and Neuromodulation, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.

出版信息

Exp Ther Med. 2018 May;15(5):4157-4166. doi: 10.3892/etm.2018.5971. Epub 2018 Mar 20.

Abstract

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

摘要

口腔扁平苔藓(OLP)病变与恶性转化风险之间的关联一直是一个有争议的话题,且具有临床重要性。因此,本研究评估了p16、Ki-67、苯并咪唑不抑制的芽殖蛋白3(Bub-3)和性别决定区Y相关高迁移率族蛋白盒4(SOX4)的表达水平,以及它们作为OLP癌前生物标志物的作用。进行了一项回顾性研究,使用了OLP、口腔发育异常(OD)、皮肤扁平苔藓(CLP)和口腔纤维增生(OFH)的组织块(n = 120)。计算了每组中p16、BUB3、Ki-67和SOX4表达的阳性指数(PI)。OLP组p16的PI为20.65%,OD组为7.85%,CLP组为86.59%,OFH组为11.8%,这些组之间的差异具有统计学意义(P < 0.001)。OLP组Ki-67的PI为11.6%,OD组为14.4%,CLP组为8.24%,OFH组为5.5%,组间观察到统计学显著差异(P < 0.001)。值得注意的是,BUB3的表达水平在各组之间无统计学差异。SOX4的最高表达水平在CLP中被确定(与OLP/CLP相比,P < 0.001;与CLP/OD相比,P = 0.001)。所确定的p16和Ki-67表达水平表明,特定的OLP病变可能具有中等恶性潜能,应仔细随访。CLP中强烈的SOX4染色表明与口腔黏膜细胞相比,上皮细胞具有不同的增殖模式。这些发现表明,SOX4表达也可能与OLP和CLP的不同临床病程相关。

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