Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
J Oral Pathol Med. 2011 Apr;40(4):305-11. doi: 10.1111/j.1600-0714.2010.01000.x. Epub 2011 Jan 5.
hMLH1 is one of the major proteins of the mammalian mismatch repair system. It has been suggested that the mismatch repair machinery could be linked to p53, a tumor suppressor protein. The AgNOR technique is used to assess cell proliferation. The aim was to compare the immunoexpression of hMLH1 and p53, and AgNOR number in oral leukoplakias with different degrees of dysplasia.
Sixty-two samples were evaluated by immunohistochemistry for hMLH1 and p53, and AgNOR technique, being 17 without dysplasia, 19 with mild dysplasia, 16 with moderate dysplasia, and 10 with severe dysplasia.
hMLH1 immunoexpression showed decreasing indexes, while p53 and AgNOR showed increasing indexes from lesions with lower degrees of dysplasia to lesions with more severe dysplasia. An inverse correlation between hMLH1 and both p53 and AgNOR, and a direct correlation between p53 and AgNOR were observed.
Alterations in the immunoexpression pattern of hMLH1 and p53 seemed to be early events in oral carcinogenesis. During acquisition of a more dysplastic phenotype, keratinocytes may show diminished capacity of DNA repair and tumor suppression, as well as higher cellular proliferation, and these pathways can be somehow interconnected.
hMLH1 是哺乳动物错配修复系统的主要蛋白之一。有人提出,错配修复机制可能与肿瘤抑制蛋白 p53 有关。AgNOR 技术用于评估细胞增殖。本研究旨在比较不同异型增生程度的口腔白斑中 hMLH1 和 p53 的免疫表达以及 AgNOR 数量。
对 62 例样本进行免疫组织化学 hMLH1 和 p53 以及 AgNOR 检测,其中无异型增生 17 例,轻度异型增生 19 例,中度异型增生 16 例,重度异型增生 10 例。
hMLH1 的免疫表达指数逐渐降低,而 p53 和 AgNOR 的免疫表达指数则逐渐升高,从异型增生程度较低的病变到异型增生程度较高的病变。hMLH1 与 p53 和 AgNOR 之间呈负相关,p53 与 AgNOR 之间呈正相关。
hMLH1 和 p53 的免疫表达模式改变似乎是口腔癌变的早期事件。在获得更具异型增生表型的过程中,角质形成细胞可能表现出 DNA 修复和肿瘤抑制能力下降,以及更高的细胞增殖能力,这些途径可能存在一定的相互关联。