Division of Surgical, Molecular, and Ultrastructural Pathology, University of Pisa and Pisa University Hospital, Pisa, Italy.
Am J Pathol. 2011 Oct;179(4):2083-90. doi: 10.1016/j.ajpath.2011.06.046. Epub 2011 Aug 18.
A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic tissue, thyroid and colon carcinoma, and blood samples from healthy donors. MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of nine patients were analyzed by real-time quantitative PCR, revealing a different viral load correlated with stage of progression. Furthermore, as never previously described, the presence of MMTVels was investigated by chromogenic in situ hybridization. MMTVels were found in 19% of normal epithelial cells collateral to a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were found in the control samples. Quantitative PCR and chromogenic in situ hybridization confirmed these results. These data could contribute to our understanding of the role of MMTVels in HBC.
几十年来,自从发现鼠乳腺肿瘤病毒(MMTV)以来,人们一直推测人类乳腺癌(HBC)的病毒病因。在 30%到 40%的浸润性 HBC 中检测到 MMTV env 样外源性序列(MMTVels),这增加了人们对这一假说的关注。在癌症进展过程中寻找 MMTVels 可能有助于更好地了解它们在 HBC 中的作用。在此,我们分析了 HBC 前浸润性病变中 MMTVels 的存在情况。通过对 FFPE 组织进行激光显微切割获得样本:20 例普通型导管增生、22 例非典型导管增生(ADH)、49 例导管原位癌(DCIS)、20 例浸润性导管癌(IDC)和 26 例 DCIS 或 IDC 旁的正常上皮细胞。对照包括还原性乳房成形术组织、甲状腺和结肠癌以及来自健康供体的血液样本。通过荧光巢式 PCR 检测 MMTVels。对来自 9 名患者的组织的 DNA 样本进行实时定量 PCR 分析,揭示了与进展阶段相关的不同病毒载量。此外,正如以前从未描述过的那样,通过显色原位杂交研究了 MMTVels 的存在情况。在 DCIS 或 IDC 旁的正常上皮细胞中发现了 19%、ADH 中发现了 27%、DCIS 中发现了 82%和 IDC 中发现了 35%的 MMTVels。对照样本中未发现 MMTVels。定量 PCR 和显色原位杂交证实了这些结果。这些数据有助于我们了解 MMTVels 在 HBC 中的作用。