Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.
Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.
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通过研究侵入性乳腺癌患者中个体内DCIS异质性来鉴定高攻击性的DCIS亚组。
DOI：
10.1371/journal.pone.0100488
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Pape-Zambito D;Jiang Z;Wu H;Devarajan K;Slater CM;Cai KQ;Patchefsky A;Daly MB;Chen X
在同一患者中诊断为浸润性导管癌（IDC）的多个导管原位癌（DCIS）病变之间的异质性尚未得到很好的评估，因此个体内DCIS异质性的研究意义尚待探讨。本研究对36例同时诊断为DCIS和IDC的患者进行福尔马林固定石蜡包埋切片的免疫组织化学评价。然后从每位患者随机选择10个DCIS病变并评分。我们的研究结果显示，同一患者的DCIS病变中PR、HER2、Ki-67和p16的表达差异显著（PR P<0.05； HER2、Ki-67和p16 P<1×10−8）。此外，72%的个体具有至少2/6标记物的异质表达。重要的是，通过将DCIS分子亚型与相邻正常末端导管小叶单位（TDLU）和IDC的分子亚型进行比较，评估不同DCIS亚组中有希望的DCIS风险生物标志物（Ki-67， p53和p16）的表达，我们的结果表明存在一个高度侵袭性的DCIS亚组，其分子亚型与相邻正常末端导管小叶单位（TDLU）和IDC相同，但与相邻正常TDLU不同。通过采用系统的方法，我们的结果清楚地表明，DCIS的个体异质性在同时诊断为IDC的患者中非常普遍。我们关于具有侵袭性特征的DCIS亚群的新发现将为乳腺肿瘤进展的机制研究提供新的范式，并且对预防研究具有广泛的意义，因为在许多其他类型的癌症中存在异质性侵袭前病变。
The heterogeneity among multiple ductal carcinoma in situ (DCIS) lesions within the same patient also diagnosed with invasive ductal carcinoma (IDC) has not been well evaluated, leaving research implications of intra-individual DCIS heterogeneity yet to be explored. In this study formalin-fixed paraffin embedded sections from 36 patients concurrently diagnosed with DCIS and IDC were evaluated by immunohistochemistry. Ten DCIS lesions from each patient were then randomly selected and scored. Our results showed that expression of PR, HER2, Ki-67, and p16 varied significantly within DCIS lesions from a single patient (P<0.05 for PR; P<1×10−8 for HER2, Ki-67 and p16). In addition, seventy-two percent of the individuals had heterogeneous expression of at least 2/6 markers. Importantly, by evaluating the expression of promising DCIS risk biomarkers (Ki-67, p53 and p16) among different DCIS subgroups classified by comparing DCIS molecular subtypes with those of adjacent normal terminal duct lobular units (TDLU) and IDC, our results suggest the existence of a highly-aggressive DCIS subgroup, which had the same molecular subtype as the adjacent IDC but not the same subtype as the adjacent normal TDLU. By using a systematic approach, our results clearly demonstrate that intra-individual heterogeneity in DCIS is very common in patients concurrently diagnosed with IDC. Our novel findings of a DCIS subpopulation with aggressive characteristics will provide a new paradigm for mechanistic studies of breast tumor progression and also have broad implications for prevention research as heterogeneous pre-invasive lesions are present in many other cancer types.
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影响因子：
3.8
作者：
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通讯作者：
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作者：
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Schnitt, SJ