Gene Expression Differences between Ductal Carcinoma in Situ with and without Progression to Invasive Breast Cancer
Gene Expression Differences between Ductal Carcinoma in Situ with and without Progression to Invasive Breast Cancer
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DOI：
10.1016/j.ajpath.2017.03.012
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发表时间：
2017-07-01
影响因子：
6
通讯作者：
van Deurzen, Carolien H. M.
中科院分区：
文献类型：
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作者：
Doebar, Shusma C.;Sieuwerts, Anieta M.;van Deurzen, Carolien H. M.
为了了解导致导管原位癌(DCIS)进展的分子改变，我们比较了单纯DCIS患者和DCIS合并同步浸润性乳腺癌(IBC)患者。12名广泛的单纯DCIS患者被纳入为具有有限侵袭能力的惰性病变的代表。这些病例与12例具有有限DCIS成分和IBC的患者相匹配，代表了具有高侵袭性潜力的病变。匹配包括年龄和代孕DCIS亚型。对DCIS细胞进行基因表达谱分析，以确定这两组之间的转录差异。用免疫组织化学方法对鉴定的基因进行了验证。有9个基因的表达存在显著差异。这些基因多数在食管癌中高表达，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在单纯食管癌中表达较高(P=0.015和P=0.028)。这种差异仅在SCGB1D2有显著意义(P=0.009)。系统聚类法显示了有无侵袭患者的明显聚集性。单纯DCIS患者与DCIS和同步IBC患者相比有不同的基因表达模式。这些基因可能定位于在DCIS进展中起重要作用的驱动通路(S)。
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.