Doebar Shusma C, Sieuwerts Anieta M, de Weerd Vanja, Stoop Hans, Martens John W M, van Deurzen Carolien H M
Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Am J Pathol. 2017 Jul;187(7):1648-1655. doi: 10.1016/j.ajpath.2017.03.012.
To understand the molecular alterations driving the progression of ductal carcinoma in situ (DCIS), we compared patients with pure DCIS and patients with DCIS and synchronous invasive breast cancer (IBC). Twelve patients with extensive pure DCIS were included as a representation of indolent lesions with limited invasive capacity. These cases were matched with 12 patients with a limited DCIS component and IBC, representing lesions with a high invasive potential. Matching included age and surrogate DCIS subtypes. Gene expression profiling was performed on DCIS cells to identify transcriptional differences between these two groups. The identified genes were validated by immunohistochemistry. Nine genes showed significantly different expression. Most of these genes were highly expressed in DCIS samples with IBC, including PLAU (P = 0.002), COL1A1 (P = 0.006), KRT81 (P = 0.009), S100A7 (P = 0.015), SCGB1D2 (P = 0.023), KRT18 (P = 0.029), and NOTCH3 (P = 0.044), whereas EGFR and CXCL14 showed a higher expression in cases with pure DCIS (P = 0.015 and P = 0.028, respectively). This difference was only significant for SCGB1D2 (P = 0.009). Hierarchical clustering revealed distinct clustering of patients with and without invasion. Patients with pure DCIS have a different gene expression pattern as compared to patients with DCIS and synchronous IBC. These genes may pinpoint to driver pathway(s) that play an important role in DCIS progression.
为了解驱动导管原位癌（DCIS）进展的分子改变，我们比较了单纯DCIS患者与合并DCIS及同步浸润性乳腺癌（IBC）的患者。纳入12例广泛单纯DCIS患者，作为侵袭能力有限的惰性病变的代表。这些病例与12例DCIS成分有限且合并IBC的患者相匹配，后者代表具有高侵袭潜能的病变。匹配因素包括年龄和替代DCIS亚型。对DCIS细胞进行基因表达谱分析，以确定两组之间的转录差异。通过免疫组织化学对鉴定出的基因进行验证。9个基因显示出显著不同的表达。这些基因中的大多数在合并IBC的DCIS样本中高表达，包括PLAU（P = 0.002）、COL1A1（P = 0.006）、KRT81（P = 0.009）、S100A7（P = 0.015）、SCGB1D2（P = 0.023）、KRT18（P = 0.029）和NOTCH3（P = 0.044），而EGFR和CXCL14在单纯DCIS病例中表达较高（分别为P = 0.015和P = 0.028）。这种差异仅对SCGB1D2有统计学意义（P = 0.009）。层次聚类显示有侵袭和无侵袭患者的明显聚类。与合并DCIS及同步IBC的患者相比，单纯DCIS患者具有不同的基因表达模式。这些基因可能指向在DCIS进展中起重要作用的驱动通路。
