In a previous study, using differential display
reverse transcriptase-PCR (DDRT-PCR) we showed that down-regulation of the PHLDA1 (
pleckstrin homology-like domain, family A, member 1; also named TDAG51)
mRNA was down-regulated in
breast tumors compared with normal breast tissue. The present study was conducted to determine the expression pattern and predictive prognostic value of PHLDA1 in
breast cancer. A series of 720 primary invasive
breast tumors were examined for PHLDA1 expression. PHLDA1
mRNA expression was determined in 74
breast tumors using quantitative Real Time PCR analysis (qPCR). PHLDA1
protein expression was evaluated by immunohistochemistry (IHC) using Tissue Microarrays (TMA) containing 699 primary invasive
breast tumors. Reduced PHLDA1
mRNA expression was identified in 72% (53/74) of the primary
breast tumors analyzed. Seventy-three percent (512/699) of cases analyzed showed negative PHLDA1
protein expression. Down-regulation of PHLDA1
protein was a strong predictor of poor prognosis for
breast cancer patients.
Breast cancer patients with
tumors that were negative for PHLDA1
protein expression had shorter disease free survival (P < 0.001) and overall survival (P < 0.001) than patients with
tumors that were positive for PHLDA1
protein expression. In addition patients with
tumors exhibiting reduced PHLDA1 expression and paucity for ER had the worse outcome (P < 0.001). Multivariate analysis indicated that PHLDA1
protein expression is an independent prognostic factor of patient survival. To our knowledge, the expression pattern of PHLDA1 in
breast cancer has not previously been investigated. Our results provide strong evidence that reduced PHLDA1 expression is important in
breast cancer progression and could serve as useful prognostic marker of disease outcome.