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Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer

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Abstract

Increased expression and activation of focal adhesion kinase (FAK) was reported to be an unfavorable factor in various human cancers, including breast cancer. In order to study FAK gene status as a prognostic factor, we evaluated FAK gene copy number and FAK protein expression in invasive breast cancer. Tumors from 435 patients with invasive breast cancer were evaluated for FAK gene status using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) based on tissue array method. Survival analyses were performed using the Kaplan–Meier method in 267 patients. 42 out of 362 evaluable cases (11.6%) showed high polysomy and 22 cases (6.1%) had gene amplification by FISH. 108 out of 393 evaluable cases (27.5%) showed FAK overexpression by IHC. FAK FISH positivity was significantly associated with higher histologic grade, higher T stage, negative estrogen receptor expression, negative progesterone receptor expression and triple-negative phenotype; FAK overexpression with higher histologic grade and triple-negative phenotype. FAK overexpression was noted in 57.8% (37 of 64) of FAK FISH+ cases. The concordance of FISH and IHC results for FAK gene was observed in 74.9% (271 of 362). Survival analyses revealed the patients with FAK FISH+ breast cancer had significantly shorter overall survival and relapse-free survival compared to those with FISH− breast cancer. In node-positive breast cancer patients who received postoperative systemic treatment, the patients with FAK FISH+ showed significantly shorter 5-year survival rates. Despite of high significant concordance between the results of FISH and IHC for FAK gene in invasive breast cancer, only FAK FISH positivity was an unfavorable prognostic factor.

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Acknowledgments

This study was supported by the Korea Breast Cancer Foundation (2009). We thank Hye Jung Lee, Sat Pyul Kim, and Seung Hee Jung for their contributions to tissue array construction, FISH, and immunohistochemical studies.

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Authors and Affiliations

  1. Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Cha Kyong Yom & Dong-Young Noh

  2. Department of Pathology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Woo Ho Kim

  3. Department of Pathology, KEPCO Medical Foundation, Hanil General Hospital, Dobong-gu Ssangmundong 388-1, Seoul, 110-746, Korea

    Hee Sung Kim

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  1. Cha Kyong Yom
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Correspondence to Hee Sung Kim.

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Yom, C.K., Noh, DY., Kim, W.H. et al. Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer. Breast Cancer Res Treat 128, 647–655 (2011). https://doi.org/10.1007/s10549-010-1150-2

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  • DOI: https://doi.org/10.1007/s10549-010-1150-2

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