High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype

Amy L. Lark; Chad A. Livasy; Lynn Dressler; Dominic T. Moore; Robert C. Millikan; Joseph Geradts; Mary Iacocca; David Cowan; Debbie Little; Rolf J. Craven; William Cance

doi:10.1038/modpathol.3800424

High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype

Amy L. Lark, Chad A. Livasy, Lynn Dressler, Dominic T. Moore, Robert C. Millikan, Joseph Geradts, Mary Iacocca, David Cowan, Debbie Little, Rolf J. Craven, William Cance

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

155 Scopus citations

Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and ≥90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.

Original language	English
Pages (from-to)	1289-1294
Number of pages	6
Journal	Modern Pathology
Volume	18
Issue number	10
DOIs	https://doi.org/10.1038/modpathol.3800424
State	Published - Oct 2005

Bibliographical note

Funding Information:
Research supported by NIH Grant RO1 65910 and Specialized Program of Research Excellence (SPORE) in Breast Cancer, NIH/NCI P50-CA 58223. We thank the UNC SPORE Tissue Procurement and Analysis Core Facility of the University of North Carolina Lineberger Comprehensive Cancer Center for training, technical support, and use of laboratory equipment. We also thank Jessica Tse for statistical assistance.

Funding

Research supported by NIH Grant RO1 65910 and Specialized Program of Research Excellence (SPORE) in Breast Cancer, NIH/NCI P50-CA 58223. We thank the UNC SPORE Tissue Procurement and Analysis Core Facility of the University of North Carolina Lineberger Comprehensive Cancer Center for training, technical support, and use of laboratory equipment. We also thank Jessica Tse for statistical assistance.

Funders	Funder number
NCI/NIH	P50-CA 58223
National Institutes of Health (NIH)	RO1 65910
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	P50CA058223
National Childhood Cancer Registry – National Cancer Institute

Keywords

Breast cancer
Focal adhesion kinase
Immunohistochemistry

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/modpathol.3800424

Cite this

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title = "High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype",

abstract = "Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and ≥90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.",

keywords = "Breast cancer, Focal adhesion kinase, Immunohistochemistry",

author = "Lark, {Amy L.} and Livasy, {Chad A.} and Lynn Dressler and Moore, {Dominic T.} and Millikan, {Robert C.} and Joseph Geradts and Mary Iacocca and David Cowan and Debbie Little and Craven, {Rolf J.} and William Cance",

note = "Funding Information: Research supported by NIH Grant RO1 65910 and Specialized Program of Research Excellence (SPORE) in Breast Cancer, NIH/NCI P50-CA 58223. We thank the UNC SPORE Tissue Procurement and Analysis Core Facility of the University of North Carolina Lineberger Comprehensive Cancer Center for training, technical support, and use of laboratory equipment. We also thank Jessica Tse for statistical assistance.",

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doi = "10.1038/modpathol.3800424",

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volume = "18",

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AU - Lark, Amy L.

AU - Livasy, Chad A.

AU - Dressler, Lynn

AU - Moore, Dominic T.

AU - Millikan, Robert C.

AU - Geradts, Joseph

AU - Iacocca, Mary

AU - Cowan, David

AU - Little, Debbie

AU - Craven, Rolf J.

AU - Cance, William

N1 - Funding Information: Research supported by NIH Grant RO1 65910 and Specialized Program of Research Excellence (SPORE) in Breast Cancer, NIH/NCI P50-CA 58223. We thank the UNC SPORE Tissue Procurement and Analysis Core Facility of the University of North Carolina Lineberger Comprehensive Cancer Center for training, technical support, and use of laboratory equipment. We also thank Jessica Tse for statistical assistance.

PY - 2005/10

Y1 - 2005/10

N2 - Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and ≥90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.

AB - Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and ≥90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.

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High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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