Paxillin, a cytoskeletal focal adhesion adaptor
protein, has been shown to be transcriptionally up-regulated and phosphorylated by human
epidermal growth factor receptor-2 (HER2) signaling in vitro.
Paxillin expression may also correlate with HER2 amplification in
breast cancer patients. In the current study, we sought to explore the relationship further between
paxillin expression and clinicopathologic features and clinical outcome in
breast cancer. A total of 314 primary invasive
breast carcinomas were assessed for
paxillin expression via immunohistochemistry.
Paxillin immunoreactivity was compared with
estrogen receptor/
progesterone receptor status, HER2 status by
silver in situ hybridization, age,
tumor size, stage, Bloom-Richardson grade, nodal status, disease-free survival (DFS), and overall survival (OS).
Paxillin expression was identified in 27.7% of
breast carcinomas as diffuse cytoplasmic staining and the expression correlated with HER2 overexpression (p < 0.001). The influence of
paxillin on clinical outcome, in particular the response to
chemotherapy, appeared to differ depending on the HER2 status of the
tumor. For the subset of HER2 nonamplified cases treated with
chemotherapy, patients whose
tumor showed a loss of
paxillin expression demonstrated a significantly lengthened DFS and OS. In contrast, loss of
paxillin expression in the HER2 amplified subset of patients who received
chemotherapy correlated with a significantly worse outcome. These data suggest that
paxillin up-regulation may be a part of the HER2 pathway in some breast
cancers and, furthermore,
paxillin expression may also influence the clinical response to
chemotherapy, depending upon the HER2 status of a given patient's
tumor. Further study of a role for
paxillin expression in predicting response to cytotoxic regimens or targeted treatments is warranted.