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Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis

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Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in a subset of invasive breast cancers. FAK transmits signals that mediate several functions including tumor cell proliferation, migration, adhesion and survival. We used immunohistochemical techniques to assess FAK expression in patients with fibrocystic disease (FCD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained from 119 patients (12 FCD, 38 ADH, 51 DCIS and 18 IDC). The anti-FAK 4.47 monoclonal antibody was used to detect FAK expression. FAK expression was scored as high (3 or 4 intensity and ≥90 positive cells) or low. The DCIS tissue sections demonstrated high FAK expression in 34/51 (66) of the sections. High FAK expression was demonstrated in 6/18 (33) of the IDC tissue sections and 8/38 (21)of the ADH tissue sections. None (0/12) of the FCD tissues sections stained high for FAK. The pattern of FAK expression in DCIS was significantly higher than ADH (p < 0.0001) and IDC (p =0.02). We conclude that FAK overexpression in preinvasive, DCIS tumors precedes tumor cell invasion or metastasis, suggesting that FAK may function as a survival signal and be an early event in breast tumorigenesis.

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Authors and Affiliations

  1. Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC

    Harry M. Lightfoot & William G. Cance

  2. Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC

    Amy Lark & Chad A. Livasy

  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC

    Dominic T. Moore, David Cowan & Lynn Dressler

  4. Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY

    Rolf J. Craven

  5. Departments of Surgery and Biochemistry, University of Florida, 1600 SW Archer Road, P.O. Box 100286, Gainesville, FL, 32610-0286, USA

    William G. Cance

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  1. Harry M. Lightfoot
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Lightfoot, H.M., Lark, A., Livasy, C.A. et al. Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis. Breast Cancer Res Treat 88, 109–116 (2004). https://doi.org/10.1007/s10549-004-1022-8

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