Elsevier

Human Pathology

Volume 34, Issue 3, March 2003, Pages 240-245
Human Pathology

Original Contributions
Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas

https://doi.org/10.1053/hupa.2003.40Get rights and content

Abstract

Integrins mediate cell adhesion to extracellular matrix and stimulate signals involved in cell proliferation, survival, and migration. Focal adhesion kinase (FAK) is considered the central molecule in integrin-mediated signaling. Previously, FAK has been implicated in invasive tumor behavior based on Northern or Western blot (immunoblot) using total tumor tissue homogenates. We used immunohistochemistry to demonstrate FAK expression in benign cervical epithelium, dysplasia, carcinoma in situ (CIS), and invasive cervical squamous cell carcinomas (SCCs), as well as in benign breast tissue, atypical ductal hyperplasia, and ductal carcinoma in situ (DCIS) and invasive carcinomas of the breast. We also used polymerase chain reaction to analyze whether infection with the high-risk human papillomavirus (HPV) subtypes correlated with FAK overexpression in CIS of the cervix. We found minimal FAK expression in benign cervical and breast epithelium and in low-grade squamous dysplasia (CIN I and CIN I-II) of the cervix, and variable FAK expression in CIS lesions of the cervix (10 of 14 cases). Most of the invasive SCCs of the cervix (13 of 16 cases) and DCIS of the breast (6 of 8 cases) were positive for FAK. Surprisingly, all DCIS of the breast were also strongly positive (7 of 7). Only 3 of 13 cases of atypical ductal hyperplasia were focally positive for FAK. Regardless of the intensity of FAK staining, all CIS of the cervix were positive for either HPV 16 or 18. We conclude that FAK overexpression is not restricted to invasive phenotype, but rather appears to be a marker for malignant transformation. Hum Pathol 34:240-245. Copyright 2003 Elsevier Inc. All rights reserved.

Section snippets

Immunohistochemistry

The cases were retrieved from the files of the Montefiore Medical Center Department of Pathology. Sixty cases were evaluated for FAK expression, including 17 cases of cervical dysplasia (CIN I and CIN I-II), 14 cases of carcinoma in situ (CIS) of the cervix, and 16 cases of invasive SCC of the cervix. In addition, 13 cases of atypical ductal hyperplasia of the breast, 8 cases of invasive carcinoma and 7 cases of ductal carcinoma in situ (DCIS) of the breast, and 4 cases of benign breast tissue

FAK expression in cervical carcinoma

Routine histological analysis and grading of all lesions was performed before immunohistochemical analysis of FAK expression. Of the 16 cases of invasive SCC of the cervix, 50% were graded as poorly differentiated tumors and the 50% as moderately differentiated tumors. Two cases of moderately differentiated SCC and 2 cases of poorly differentiated SCC contained normal squamous epithelium on the same slide that served as internal controls. Thirteen of 16 cases of invasive SCC stained strongly

Discussion

A large body of evidence supports the role of FAK in regulation of cell proliferation, survival, and migration. Detailed molecular analyses have demonstrated that the versatility of FAK functions is due to its unique structure that enables it to act as a “scaffold” for the assembly of the multiprotein signaling complexes.7, 8 Thus FAK acts as a linker of transmembrane receptors with the major growth regulatory pathways, including extracellular signal-related kinase and c-Jun-N-terminal

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