Khalil Antoine A, Ilina Olga, Gritsenko Pavlo G, Bult Peter, Span Paul N, Friedl Peter
Department of Dermatology and Graduate School of Life Sciences, University of Würzburg, Würzburg, Germany.
Department of Cell Biology, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
Clin Exp Metastasis. 2017 Oct;34(6-7):421-429. doi: 10.1007/s10585-017-9858-6. Epub 2017 Sep 11.
Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and "Indian files" in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell-cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination.
乳腺癌会发生集体性组织侵袭，在实验模型中，还能发生集体性转移。然而，集体性侵袭在临床疾病中的发生率及其对远处转移的作用仍不清楚。我们在此对原发性浸润性导管癌（IDC）和E-钙黏蛋白阴性的浸润性小叶癌（ILC）的脂肪组织侵袭情况进行评分，并确定这两种癌症类型中主要为集体性侵袭模式（86/86个样本）。尽管IDC病变中的集体性侵袭保留了黏附连接，但ILC中的多细胞簇和“印度队列”，尽管缺乏黏附连接（AJ）蛋白E-钙黏蛋白和β-连环蛋白，但在细胞间接触处保留了CD44。通过组织形态学评分和半自动图像分析，我们发现脂肪组织中集体性侵袭的程度与远处无转移生存期的降低相关（5年随访；风险比分别为2.32和2.29）。因此，集体性侵袭是乳腺癌的主要侵袭模式，在IDC和ILC中形成不同的连接亚型，并与远处转移相关，提示其在全身播散中起关键作用。
