Institute of Maternal and Children's Sciences-Urology, Polytechnic University of the Marche Region - Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
Department of Molecular Pathology and Innovative Therapies-Histology, Polytechnic University of the Marche Region, Ancona, Italy.
J Cell Mol Med. 2009 Aug;13(8B):2115-2121. doi: 10.1111/j.1582-4934.2008.00482.x. Epub 2008 Aug 21.
Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin-embedded sections, using anti-5-methylcytosine (5mc) and anti-Acetyl-Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P = 0.033), whereas the percentage of histone acetylation was significantly lower (P = 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.
手术是治疗肾细胞癌（RCC）的主要方法；对于小的外周病变，可以进行保肾手术作为治疗选择。表观遗传学构成了一种新的实体，通过甲基化、乙酰化和染色质重塑来调节基因表达。除了由于突变、杂合性丢失或经典遗传事件导致的沉默外，表观遗传修饰标志着癌发生和肿瘤发展过程中的重要事件。我们研究了一系列小的常规透明细胞肾细胞癌（即小于 5 厘米）（pT1a）患者在接受部分肾切除术治疗后，整体甲基化和组蛋白乙酰化表达情况，以评估其作为诊断生物标志物的可能作用。总共选择了 54 例常规单一 RCC 患者进行部分肾切除术治疗，并随访了 186 个月。使用抗 5-甲基胞嘧啶（5mc）和抗乙酰化组蛋白 H3（Lys 9）对石蜡包埋切片进行免疫组织化学染色。我们的结果证实，肿瘤组织中细胞整体甲基化的平均百分比明显高于肿瘤周围组织，而肿瘤组织中细胞组蛋白乙酰化的平均百分比明显较低。在 3 级和 4 级中，甲基化的百分比明显较高（P = 0.033），而组蛋白乙酰化的百分比明显较低（P = 0.023），因此这些标志物可能与 pT1a RCC 的肿瘤侵袭性相关。在与不同考虑因素相关的患者生存的单因素分析中，Fuhrman 分级是最重要的生存因素。这些表观遗传标记可以为我们提供关于 RCC 中染色质重塑的有趣信息；整体甲基化百分比随着 Fuhrman 分级的增加而增加，而组蛋白乙酰化随着分级的增加而降低；我们的结果表明，整体高甲基化和组蛋白低乙酰化可以被认为是 RCC 的早期事件，并与肿瘤侵袭性相关。
