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Atypical E-cadherin expression in cell clusters overlying focally disrupted mammary myoepithelial cell layers: Implications for tumor cell motility and invasion
Authors:Xichen Zhang  Shahreyar Shar Hashemi  Morvarid Yousefi  Chunling Gao  Joy Sheng  Jinsong Ni  Wan Wang  Jeffrey Mason  Yan-gao Man
Affiliation:1. College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin, China;2. Departments of Surgery and Internal Medicine, Staten Island University Hospital, NY, USA;3. Division of Monoclonal Antibodies, Food and Drug Administration, Bethesda, MD, USA;4. Real-time PCR Technical Support Department, Applied Biosystems, Foster City, CA, USA;5. Norman Bethune College of Medical Science, Jilin University, Changchun, Jilin, China;6. Breast and Thyroid Surgery Department, China-Japan Union Hospital, Changchun, Jilin, China;g Department of Biophysics, Armed Forces Institute of Pathology, Rockville, MD, USA;h Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and American Registry of Pathology, 6825, 16th Street, NW, Washington, DC 20306-6000, USA
Abstract:Our recent studies showed that cell clusters overlying focal myoepithelial cell layer disruptions (FMCLD) had a significantly higher rate of ER negativity, genetic instabilities, and expression of invasion-related genes than adjacent cells within the same duct. This study attempted to determine if these cells would show aberrant E-cadherin expression, which imparts greater propensity for cell motility and invasion. Consecutive sections from breast tumors with a high frequency of FMCLD were double-immunostained for E-cadherin and a panel of related markers. The E-cadherin mRNA levels in cells overlying FMCLD and adjacent cells within the same duct were compared using real-time PCR. Nearly all the cell clusters overlying FMCLD were strongly immunoreactive for E-cadherin, whereas their adjacent counterparts within the same duct were largely negative. Cell clusters overlying FMCLD were generally arranged as tongue-like projections, “puncturing” deep into the stroma or tube-like structures that often contained red blood cells. The sub-cellular localization of E-cadherin in the above structures, however, was primarily cytoplasmic. The mRNA level of E-cadherin in cell clusters overlying FMCLD was significantly higher than that in adjacent cells within the same duct. These findings suggest that aberrant expression of E-cadherin may contribute to cell motility and invasion.
Keywords:E-cadherin   Breast cancer invasion   Myoepithelial cell layer disruption   Epithelial-stromal-interaction   Double immunohistochemistry
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