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Int J Biol Sci 2008; 4(5):259-269. doi:10.7150/ijbs.4.259 This issue Cite

Research Paper

Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers: a trigger or sign for emergence of more aggressive cell clones?

Xichen Zhang¹, Shahreyar Shar Hashemi², Morvarid Yousefi², Jinsong Ni³, Qiuyue Wang¹, Ling Gao¹, Pengtao Gong¹, Chunling Gao⁴, Joy Sheng⁵, Jeffrey Mason⁶, Yan-gao Man^{6 ✉}

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. Norman Bethune College of Medical Science, Jilin University, Changchun, Jilin, China
4. Division of Monoclonal Antibodies, Food and Drug Administration, Bethesda, MD, USA
5. Real-time PCR Technical Support Department, Applied Biosystems, Foster City, CA, USA
6. Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC, USA

✉ Correspondence to: Yan-gao Man, MD., PhD., Director of Gynecologic and Breast Research Laboratory, Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and American Registry of Pathology, 6825 16th Street, NW, Washington DC 20306-6000. Phone: 202-782-1612; Fax: 202-782-3939; E-mail: manosd.mil More

Abstract

Our recent studies revealed that cell clusters overlying focal myoepithelial cell layer disruption (FMCLD) had a significantly higher frequency of genetic instabilities and expression of invasion-related genes than their adjacent counterparts within the same duct. Our current study attempted to assess whether these cell clusters would also have elevated c-erbB2 expression. Human breast tumors (n=50) with a high frequency of FMCLD were analyzed with double immunohistochemistry, real-time RT-PCR, and chromogenic in situ hybridization for c-erbB2 protein and gene expression. Of 448 FMCLD detected, 404 (90.2%) were associated with cell clusters that had intense c-erbB2 immunoreactivities primarily in their cytoplasm, in contrast to their adjacent counterparts within the same duct, which had no or barely detectable c-erbB2 expression. These c-erbB2 positive cells were arranged as tongue-like projections, “puncturing” into the stroma, and about 20% of them were in direct continuity with tube-like structures that resembled blood vessels. Aberrant c-erbB2 expression was also seen in clusters of architecturally normal-appearing ducts that had distinct cytological abnormalities in both ME and epithelial cells, whereas not in their clear-cut normal counterparts. Molecular assays detected markedly higher c-erbB2 mRNA and gene amplification in cell clusters associated with FMCLD than in those associated with non-disrupted ME cell layers. Our findings suggest that cell clusters overlying FMCLD may represent the precursors of pending invasive lesions, and that aberrant cerbB2 expression may trigger or signify the emergence of biologically more aggressive cell clones.

Keywords: Tumor invasion, myoepithelial cells, c-erbB2, tumor stem cells, monoclonal proliferation

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