Altered microRNA expression confined to specific epithelial cell Subpopulations in breast cancer
Altered microRNA expression confined to specific epithelial cell Subpopulations in breast cancer
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DOI：
10.1158/0008-5472.can-07-5019
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发表时间：
2007-12-15
期刊：
影响因子：
11.2
通讯作者：
Cole, Charles N.
中科院分区：
文献类型：
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作者：
Sempere, Lorenzo F.;Christensen, Mette;Cole, Charles N.
microRNAs（miRNAs）是一类新的非编码短RNA（18-25个核苷酸），参与多种发育和病理过程。改变的miRNA表达与几种类型的人类癌症有关。然而，大多数研究没有确定miRNA表达变化是否发生在经历恶性转化的细胞中。为了深入了解乳腺癌中的miRNA失调，我们实施了原位杂交（ISH）方法来揭示来自> 100例患者病例的代表正常和肿瘤组织的福尔马林固定的石蜡包埋标本中miRNA表达的空间分布。在这里，我们报告说，miR-145和miR-205的表达仅限于正常乳腺导管和小叶的肌上皮/基底细胞区室，而它们的积累减少或完全消除在匹配的肿瘤标本。相反，其他miRNA的表达主要在正常组织的管腔上皮细胞中以不同的水平检测; miR-21的表达经常增加，而let-7a的表达在恶性细胞中减少。我们还分析了miRNA表达与上皮标志物、雌激素受体、孕激素受体和HER 2等预后指标以及临床结果数据的相关性。与大体组织活检中的miRNA表达谱相比，该ISH方法提供了一种更直接和信息量更大的评估，即改变的miRNA表达如何促进乳腺癌的发生。最重要的是，在不典型增生和原位癌病变中改变的miR-145表达的早期表现表明，这种miRNA可能具有作为早期检测的新生物标志物的潜在临床应用。
MicroRNAs (miRNAs) are a new class of short noncoding regulatory RNAs (18-25 nucleotides) that are involved in diverse developmental and pathologic processes. Altered miRNA expression has been associated with several types of human cancer. However, most studies did not establish whether miRNA expression changes occurred within cells undergoing malignant transformation. To obtain insight into miRNA deregulation in breast cancer, we implemented an in situ hybridization (ISH) method to reveal the spatial distribution of miRNA expression in archived formalin-fixed, paraffin-embedded specimens representing normal and tumor tissue from > 100 patient cases. Here, we report that expression of miR-145 and miR-205 was restricted to the myoepithelial/basal cell compartment of normal mammary ducts and lobules, whereas their accumulation was reduced or completely eliminated in matching tumor specimens. Conversely, expression of other miRNAs was detected at varying levels predominantly within luminal epithelial cells in normal tissue; expression of miR-21 was frequently increased, whereas that of let-7a was decreased in malignant cells. We also analyzed the association of miRNA expression with that of epithelial markers; prognostic indicators such as estrogen receptor, progesterone receptor, and HER2; as well as clinical outcome data. This ISH approach provides a more direct and informative assessment of how altered miRNA expression contributes to breast carcinogenesis compared with miRNA expression profiling in gross tissue biopsies. Most significantly, early manifestation of altered miR-145 expression in atypical hyperplasia and carcinoma in situ lesions suggests that this miRNA may have a potential clinical application as a novel biomarker for early detection.