Department of Histopathology, School of Molecular Medical Sciences, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
Breast Cancer Res Treat. 2012 Sep;135(2):403-13. doi: 10.1007/s10549-012-2169-3. Epub 2012 Jul 21.
Dicer is a protein that plays a pivotal role in the final steps of the microRNA (miRNA) processing pathway, to produce mature miRNAs from their precursor molecules. The purpose of the current study was to assess the biological and prognostic value of Dicer protein expression in breast cancer (BC). Dicer protein expression was assessed immunohistochemically in two sets of BC: (1) full-face sections of selected BC series with distinct stages of tumour progression (normal, in situ (DCIS), primary invasive BC and nodal metastases) to evaluate its differential expression. (2) Tissue microarray comprising a large and well-characterised series of unselected clinically annotated invasive BC (n = 1,174) to investigate its correlation with clinicopathological features and patient outcome. A gradual loss of Dicer protein expression was observed in malignant compared to normal breast tissues, with the loss being the least in DCIS and most prominent in metastatic malignant cells. In invasive BC, loss of Dicer expression was associated with features of aggressive behaviour including higher histological grade, loss of hormone receptor and BRCA1 protein expression and with shorter disease-free survival (DFS). Dicer expression was an independent predictor of recurrence in the aggressive HER2-positive subgroup. Moreover, loss of Dicer was predictive of better response to chemotherapy and to endocrine therapy. This study provides evidence that Dicer protein plays a role in human BC progression and behaviour, and assessment of its expression could provide prognostic information in BC including the HER2-positive class.
Dicer 是一种蛋白，在 microRNA（miRNA）加工途径的最后步骤中发挥关键作用，将前体分子加工为成熟的 miRNA。本研究旨在评估 Dicer 蛋白在乳腺癌（BC）中的表达的生物学和预后价值。使用两种 BC 集进行了 Dicer 蛋白免疫组织化学评估：（1）选择的具有不同肿瘤进展阶段（正常、原位（DCIS）、原发性浸润性 BC 和淋巴结转移）的 BC 系列的全脸切片，以评估其差异表达。（2）包含大量未经选择的临床注释浸润性 BC 的组织微阵列（n = 1,174），以研究其与临床病理特征和患者预后的相关性。与正常乳腺组织相比，恶性组织中观察到 Dicer 蛋白表达逐渐丧失，DCIS 中丢失最少，转移性恶性细胞中丢失最明显。在浸润性 BC 中，Dicer 表达缺失与侵袭性行为特征相关，包括更高的组织学分级、激素受体和 BRCA1 蛋白表达缺失，以及较短的无病生存期（DFS）。Dicer 表达是侵袭性 HER2 阳性亚组复发的独立预测因子。此外，Dicer 的丢失预测对化疗和内分泌治疗的反应更好。这项研究提供了证据表明 Dicer 蛋白在人类 BC 的进展和行为中发挥作用，评估其表达可以为包括 HER2 阳性类型在内的 BC 提供预后信息。
