Balleine Rosemary L, Webster Lucy R, Davis Sean, Salisbury Elizabeth L, Palazzo Juan P, Schwartz Gordon F, Cornfield Dennis B, Walker Robert L, Byth Karen, Clarke Christine L, Meltzer Paul S
Translational Oncology Sydney West Area Health Service, Australia.
Clin Cancer Res. 2008 Dec 15;14(24):8244-52. doi: 10.1158/1078-0432.CCR-08-0939.
Increased incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has emphasized the challenges of managing this condition. The aim of this study was to identify informative clinical indicators of DCIS biology by molecular profiling.
Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium were microdissected from 46 invasive breast cancers. Oligonucleotide probes showing differential expression between DCIS associated with grade 1 and 3 invasive cancer were identified by microarray-based gene expression profiling. Expression at these probes was used to define a "molecular grade" subcategorization of all samples. The genomic basis of molecular grade was examined by array-based comparative genomic hybridization. Clinical course was examined in a cohort of 134 patients with DCIS treated by surgery alone.
DCIS samples were designated as low or high molecular grade based on expression at 173 probes. The low molecular grade subgroup included low (n = 10) and intermediate (n = 11) nuclear grade DCIS as well as all samples of atypical ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear grade. The character and degree of genomic aberration were distinct between molecular grade subgroups. A classification tree model including nuclear grade and Ki67 score accurately predicted molecular grade for 95.7% of samples. In an independent cohort, this showed a pattern of rapid disease recurrence for high molecular grade DCIS.
Molecular profiling indicates a binary grading scheme for DCIS. This practical approach has potential to improve clinical evaluation of DCIS.
与乳腺癌钼靶筛查相关的导管原位癌（DCIS）发病率增加，凸显了管理这种疾病的挑战。本研究的目的是通过分子谱分析确定DCIS生物学的信息性临床指标。
从46例浸润性乳腺癌中显微切割出原位癌、非典型导管增生和良性上皮区域。通过基于微阵列的基因表达谱分析，鉴定出在与1级和3级浸润性癌相关的DCIS之间表现出差异表达的寡核苷酸探针。这些探针处的表达用于定义所有样本的“分子分级”亚分类。通过基于阵列的比较基因组杂交检查分子分级的基因组基础。在一组仅接受手术治疗的134例DCIS患者中检查临床病程。
根据173个探针处的表达，将DCIS样本指定为低分子分级或高分子分级。低分子分级亚组包括低（n = 10）和中（n = 11）核分级的DCIS以及所有非典型导管增生样本（n = 4）和良性上皮样本（n = 7）。高分子分级亚组包括中（n = 7）和高（n =
19）核分级的DCIS。分子分级亚组之间基因组畸变的特征和程度不同。一个包括核分级和Ki67评分的分类树模型准确预测了95.7%样本的分子分级。在一个独立队列中，这显示了高分子分级DCIS疾病快速复发的模式。
分子谱分析表明DCIS存在二元分级方案。这种实用方法有可能改善DCIS的临床评估。
