Research Papers:

Detecting cell-in-cell structures in human tumor samples by E-cadherin/CD68/CD45 triple staining

Hongyan Huang _, Ang Chen, Ting Wang, Manna Wang, Xiangkai Ning, Meifang He, Yazhuo Hu, Long Yuan, Shichong Li, Qiwei Wang, Hong Liu, Zhaolie Chen, Jun Ren and Qiang Sun

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Oncotarget. 2015; 6:20278-20287. https://doi.org/10.18632/oncotarget.4275

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Hongyan Huang1,2,*, Ang Chen2,*, Ting Wang3,*, Manna Wang2, Xiangkai Ning2, Meifang He2, Yazhuo Hu4, Long Yuan2, Shichong Li2, Qiwei Wang2, Hong Liu2, Zhaolie Chen2, Jun Ren1, Qiang Sun2

1Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, Beijing, P. R. China

2Laboratory of Cell Engineering, Institute of Biotechnology, Beijing, P. R. China

3Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China, Xi'an, Shaanxi Province, P. R. China

4Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Qiang Sun, e-mail: [email protected]

Jun Ren, e-mail: [email protected]

Keywords: cell-in-cell structures, cell cannibalism, EML method, epithelium, macrophage

Received: March 08, 2015     Accepted: June 08, 2015     Published: June 18, 2015


Although Cell-in-cell structures (CICs) had been documented in human tumors for decades, it is unclear what types of CICs were formed largely due to low resolution of traditional way such as H&E staining. In this work, we employed immunofluorescent method to stain a panel of human tumor samples simultaneously with antibodies against E-cadherin for Epithelium, CD68 for Macrophage and CD45 for Leukocytes, which we termed as “EML method” based on the cells detected. Detail analysis revealed four types of CICs, with tumor cells or macrophage engulfing tumor cells or leukocytes respectively. Interestingly, tumor cells seem to be dominant over macrophage (93% vs 7%) as the engulfer cells in all CICs detected, whereas the overall amount of internalized tumor cells is comparable to that of internalized CD45+ leukocytes (57% vs 43%). The CICs profiles vary from tumor to tumor, which may indicate different malignant stages and/or inflammatory conditions. Given the potential impacts different types of CICs might have on tumor growth, we therefore recommend EML analysis of tumor samples to clarify the correlation of CICs subtypes with clinical prognosis in future researches.

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