Male breast cancer (MBC) is an uncommon malignancy. We have previously reported
that the expression of the Hippo transducers TAZ/YAP and their target CTGF was
associated with inferior survival in MBC patients. Preclinical evidence
demonstrated that Axl is a transcriptional target of TAZ/YAP. Thus, we herein
assessed AXL expression to further investigate the significance of active
TAZ/YAP-driven transcription in MBC. For this study, 255 MBC samples represented
in tissue microarrays were screened for AXL expression, and 116 patients were
included. The association between categorical variables was verified by the
Pearson's Chi-squared test of independence (2-tailed) or the Fisher Exact test.
The relationship between continuous variables was tested with the Pearson's
correlation coefficient. The Kaplan-Meier method was used for estimating survival
curves, which were compared by log-rank test. Factors potentially impacting
10-year and overall survival were verified in Cox proportional regression models.
AXL was positively associated with the TAZ/CTGF and YAP/CTGF phenotypes
(p = 0.001 and p = 0.002, respectively). Patients with TAZ/CTGF/AXL- or
YAP/CTGF/AXL-expressing tumors had inferior survival compared with
non-triple-positive patients (log rank p = 0.042 and p = 0.048, respectively).
The variables TAZ/CTGF/AXL and YAP/CTGF/AXL were adverse factors for 10-year
survival in the multivariate Cox models (HR 2.31, 95%CI:1.02-5.22, p = 0.045, and
HR 2.27, 95%CI:1.00-5.13, p = 0.050). Nearly comparable results were obtained
from multivariate analyses of overall survival. The expression pattern of AXL
corroborates the idea of the detrimental role of TAZ/YAP activation in MBC.
Overall, Hippo-linked biomarkers deserve increased attention in this rare
disease. This article is protected by copyright. All rights reserved.
- Hippo Pathway
- Male Breast Cancer