Cell budding from pre-invasive tumors: Intrinsic precursor of invasive breast lesions?

Gai,Jin-Hong; Gong,Peng-Tao; Li,Jian-Hua; Man,Yan-Gao; Ni,Jin-Song; Ma,Hongxi; Hao,Fen-Yun; Zhang,Xi-Chen; Liu,Ying

doi:10.3892/etm.2011.251

Cell budding from pre-invasive tumors: Intrinsic precursor of invasive breast lesions?

Authors:
- Jin-Hong Gai
- Peng-Tao Gong
- Jian-Hua Li
- Yan-Gao Man
- Jin-Song Ni
- Hongxi Ma
- Fen-Yun Hao
- Xi-Chen Zhang
- Ying Liu
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Affiliations: Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu 730070, P.R. China, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, P.R. China, Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC 20306-6000, USA, Department of Pathologic Anatomy, School of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China, Department of Pathology, Weifang People's Hospital, Weifang, Shandong 261061, P.R. China
Published online on: April 7, 2011 https://doi.org/10.3892/etm.2011.251
Pages: 633-639

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Abstract

Our previous studies showed that in patients with ductal carcinoma in situ (DCIS) of the breast, the tumor cells that overlie focal myoepithelial cell layer disruptions (FMCLDs) are generally arranged as finger-like projections that bud into the stroma. These budding cells have significantly more genetic instability and invasion-related gene expression, and less estrogen receptor (ER) expression, than their epithelial cell counterparts. This study aimed to assess these cells for potential molecular markers that are uniquely associated with cell adhesion and motility. Seventeen ER-positive DCIS cases were screened by immunostaining for ER, and 7 cases which harbored FMCLD lesions were used to examine the expression of the potential markers. Two cases with both DCIS and invasive lesions were selected for comparing the differences in molecular expression between these lesion types. The results showed that expression levels of talin, E-cadherin and focal adhesion kinase (FAK) in tumor cells overlying FMCLDs were higher than those within the corresponding duct. Integrin β1 staining was detected only in a small number of the tumor cells overlying the FMCLDs. Vinculin staining was weak (18%) or not detected (82%), and no expression was found in the tumor cells within the corresponding duct or in the pure isolated DCIS. By contrast, the expression levels of talin, vinculin and integrin β1 in the invasive tumors were distinctly higher than those in DCIS, and the expression of FAK and E-cadherin was lower. Using electron microscopy, we found that the tight junctions between tumor cells overlying the FMCLDs were reduced compared to the adjacent tumor cells in the lumen. These results indicate that the tumor cells overlying FMCLDs are likely to represent the specific precursors of invasive breast lesions. Our findings may also facilitate the identification of specific targets for further molecular profiling, which will more completely characterize this important cell population.

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