Marzese Diego M, Gago Francisco E, Orozco Javier I, Tello Olga M, Roqué María, Vargas-Roig Laura M
School of Medical Sciences, National University of Cuyo, Parque General San Martín s/n, CP 5500, Mendoza, Argentina.
J Med Case Rep. 2011 Oct 18;5:516. doi: 10.1186/1752-1947-5-516.
Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, tumor-suppressor genes) and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non-giant breast fibroadenoma. In this particular case, there are no previously published data on epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpG islands have confirmed that the aberrant methylation is specific to malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas.
A 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in her left breast. On physical examination, a 10 × 10 cm lump was detected and axillary lymph nodes were not enlarged. After surgical removal the lump was diagnosed as a giant fibroadenoma. Because of the high growth rate of this benign tumor, we decided to analyze the methylation status of 49 CpG islands related to cell growth control. We have identified the methylation of five cancer-related CpG islands in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44.
In this case report we show for the first time the methylation analysis of a giant fibroadenoma. The detection of methylation of these five cancer-related regions indicates substantial epigenomic differences with non-giant fibroadenomas. Epigenetic alterations could explain the higher growth rate of this tumor. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there exist no previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion.
巨大纤维腺瘤是一种罕见的良性乳腺病变变体。已知启动子区域CpG岛的异常甲基化与基因（如肿瘤抑制基因）的沉默有关，并且似乎是乳腺癌发生病因学中的早期事件。在非巨大乳腺纤维腺瘤中，仅报道了p16INK4a的高甲基化。在这个特殊病例中，以前没有关于巨大纤维腺瘤表观遗传改变的 published 数据。我们之前基于对49个癌症相关CpG岛的分析结果证实，异常甲基化是恶性乳腺肿瘤特有的，在正常乳腺组织和乳腺纤维腺瘤中完全不存在。
一名13岁的西班牙裔女孩在注意到左乳房肿块逐渐增大后前来就诊。体格检查发现一个10×10 cm的肿块，腋窝淋巴结未肿大。手术切除肿块后诊断为巨大纤维腺瘤。由于这种良性肿瘤生长速度快，我们决定分析与细胞生长控制相关的49个CpG岛的甲基化状态。我们在巨大纤维腺瘤组织中鉴定出五个癌症相关CpG岛的甲基化：ESR1、MGMT、WT-1、BRCA2和CD44。
在本病例报告中，我们首次展示了巨大纤维腺瘤的甲基化分析。这五个癌症相关区域甲基化的检测表明与非巨大纤维腺瘤存在显著的表观基因组差异。表观遗传改变可以解释这种肿瘤较高的生长速度。我们的数据有助于增加对乳腺疾病中异常甲基化的了解。在这个特殊病例中，以前没有关于甲基化在巨大纤维腺瘤中作用的数据，巨大纤维腺瘤根据定义被认为是一种良性乳腺病变。
