Walker Logan C, Harris Gavin C, Holloway Andrew J, McKenzie Grant W, Wells J Elisabeth, Robinson Bridget A, Morris Christine M
Cancer Genetics Research Group, Department of Pathology, University of Otago at Christchurch, Christchurch, New Zealand.
Cancer Genet Cytogenet. 2007 Oct 15;178(2):94-103. doi: 10.1016/j.cancergencyto.2007.06.002.
Invasive ductal carcinomas of the breast (IDC) are routinely assessed on hematoxylin and eosin stained paraffin sections, with limited use of immunohistochemistry (IHC). Most IDC are regarded as a single diagnostic entity, IDC of no special type (IDC-NST), which is subdivided further only by grading. However, recent research suggests that there is high clinical relevance in differentiating IDC subtypes. Here, we ascertain whether tumor histology alone can predict basal or luminal cell phenotype in high-grade IDC-NST, and whether IHC and molecular characteristics are associated with the observed morphologies. A total of 29 grade 3 IDC-NST samples were studied, 10 tumors from a selected pilot cohort A and 19 tumors from an unselected validation cohort B. Along with histopathological assessment, the expression of ESR1, PGR, ERBB2 (HER-2), the basal/myoepithelial marker TP73L (p63), cytokeratins 5/6 (KRT5/6) and 14 (KRT14), and the luminal-specific cytokeratins 8/18 (KRT 8/18) and 19 (KRT19) was assessed by IHC. Hierarchical cluster analysis of clinicopathological variables and, separately, microarray expression profiles showed that the phenotypically distinctive basaloid and luminal tumors of cohort A fell into two main groups, defined by heterogeneous or uniformly positive expression of KRT8/18. The 38 genes differentially expressed between these two classes included ERBB2, KRT8, and six other genes previously associated with ERBB2-positive or luminal phenotypes. Tumor histology was not predictive for validation cohort B, but quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed two molecularly defined clusters that again aligned with the KRT8/18 staining phenotypes. Metaphase comparative genomic hybridization revealed 10q, 16q, and 20q copy-number imbalances that associated recurrently with KRT8/18 staining patterns.
乳腺浸润性导管癌（IDC）通常在苏木精和伊红染色的石蜡切片上进行评估，免疫组织化学（IHC）的应用有限。大多数IDC被视为单一诊断实体，即非特殊类型的IDC（IDC-NST），仅通过分级进一步细分。然而，最近的研究表明，区分IDC亚型具有高度临床相关性。在此，我们确定仅肿瘤组织学能否预测高级别IDC-NST中的基底或管腔细胞表型，以及IHC和分子特征是否与观察到的形态相关。共研究了29个3级IDC-NST样本，其中10个肿瘤来自选定的试点队列A，19个肿瘤来自未选定的验证队列B。除了组织病理学评估外，还通过IHC评估了ESR1、PGR、ERBB2（HER-2）、基底/肌上皮标志物TP73L（p63）、细胞角蛋白5/6（KRT5/6）和14（KRT14）以及管腔特异性细胞角蛋白8/18（KRT 8/18）和19（KRT19）的表达。对临床病理变量进行层次聚类分析，并分别对微阵列表达谱进行分析，结果显示队列A中表型独特的基底样和管腔肿瘤分为两个主要组，由KRT8/18的异质性或均匀阳性表达定义。这两类之间差异表达的38个基因包括ERBB2、KRT8以及其他六个先前与ERBB2阳性或管腔表型相关的基因。肿瘤组织学对验证队列B无预测性，但定量实时聚合酶链反应（qRT-PCR）分析揭示了两个分子定义的簇，它们再次与KRT8/18染色表型一致。中期比较基因组杂交揭示了与KRT8/18染色模式反复相关的10q、16q和20q拷贝数失衡。
