Single-cell heterogeneity in ductal carcinoma in situ of breast.
Single-cell heterogeneity in ductal carcinoma in situ of breast.
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DOI：
10.1038/modpathol.2017.143
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Badve SS
中科院分区：
文献类型：
--
作者：
Gerdes MJ;Gökmen-Polar Y;Sui Y;Pang AS;LaPlante N;Harris AL;Tan PH;Ginty F;Badve SS
侵袭性癌症中突变和RNA表达的异质性模式已得到充分记录。然而，技术挑战限制了研究蛋白质表达异质性的能力。对于浸润前病变，如乳腺导管原位癌，尤其如此。使用11种疾病相关标志物（EGFR、HER 2、HER 4、S6、pmTOR、CD 44 v6、SLC 7A 5和CD 10、CD 4、CD 8和CD 20，加上用于细胞分割的泛细胞角蛋白、泛钙粘蛋白、DAPI、Na+K+ ATP酶）的多重免疫荧光分析，在单个5 μ m组织切片中分析导管原位癌中的细胞水平异质性。使用单细胞分割算法在细胞水平定量表达。使用K均值聚类来确定上皮细胞标志物和免疫标志物的共表达模式。我们首次记录了导管内、导管间和导管原位癌患者间上皮细胞异质性的存在。每个导管内8个簇的分布存在中度异质性（平均Shannon指数0.76;范围0 - 1.61）。此外，在每名患者中，所有导管的平均Shannon指数范围为0.33至1.02（S.D. 0.09 0.38）。由于导管内的聚类分布不均匀，对8个导管的分析可能足以代表所有聚类，即导管内和导管间异质性。上皮细胞聚集的模式与免疫浸润的存在和类型相关，表明每个患者的上皮肿瘤和免疫系统之间存在复杂的相互作用。这项分析还提供了第一个证据，同时分析上皮和免疫/基质成分可能是必要的，以了解复杂的环境中导管原位癌病变。
Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell level heterogeneity in ductal carcinoma in situ was analyzed in a single 5um tissue section using multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, Na+K+ATPase for cell segmentation). Expression was quantified at cell level using a single cell segmentation algorithm. K-means clustering was used to determine co-expression patterns of epithelial cell markers and immune markers. We document for the first time the presence of epithelial cell heterogeneity within ducts, between ducts and between patients with ductal carcinoma in situ. There was moderate heterogeneity in a distribution of 8 clusters within each duct (average Shannon Index 0.76; ranged 0 – 1.61). Furthermore, within each patient, the average Shannon Index across all ducts ranged from 0.33 to 1.02 (S.D. 0.09 to 0.38). As the distribution of clusters within ducts was uneven, the analysis of 8 ducts might be sufficient to represent all the clusters i.e. within- and between-duct heterogeneity. The pattern of epithelial cell clustering was associated with the presence and type of immune infiltrates, indicating a complex interaction between the epithelial tumor and immune system for each patient. This analysis also provides the first evidence that simultaneous analysis of both the epithelial and immune/stromal components might be necessary to understand the complex milieu in ductal carcinoma in situ lesions.
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影响因子：
3.1
作者：
Juhász C;Nahleh Z;Zitron I;Chugani DC;Janabi MZ;Bandyopadhyay S;Ali-Fehmi R;Mangner TJ;Chakraborty PK;Mittal S;Muzik O
通讯作者：
Muzik O
影响因子：
--
作者：
Buckley N;Boyle D;McArt D;Irwin G;Harkin DP;Lioe T;McQuaid S;James JA;Maxwell P;Hamilton P;Mullan PB;Salto-Tellez M
通讯作者：
Salto-Tellez M
影响因子：
45.3
作者：
Adams, Sylvia;Gray, Robert J.;Badve, Sunil S.
通讯作者：
Badve, Sunil S.
DOI：
10.1097/pai.0b013e318047df6d
发表时间：
2008-03-01
影响因子：
1.6
作者：
Afify, Alaa;McNiel, Maaya A.;Paulino, Augusto F.
通讯作者：
Paulino, Augusto F.
影响因子：
--
作者：
SHANNON, CE
通讯作者：
SHANNON, CE