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Title of Journal: Breast Cancer Res Treat

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Abbravation: Breast Cancer Research and Treatment

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Springer US

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DOI

10.1002/bip.1969.360080514

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ISSN

1573-7217

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Downregulation of Emphasis Type="Italic"PHLDA1

Authors: Maria Aparecida Nagai José Humberto T G Fregnani Mário Mourão Netto Maria Mitzi Brentani Fernando A Soares
Publish Date: 2007/01/09
Volume: 106, Issue: 1, Pages: 49-56
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Abstract

In a previous study using differential display reverse transcriptasePCR DDRTPCR we showed that downregulation of the PHLDA1 pleckstrin homologylike domain family A member 1 also named TDAG51 mRNA was downregulated 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 Seventythree percent 512/699 of cases analyzed showed negative PHLDA1 protein expression Downregulation 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  0001 and overall survival P  0001 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  0001 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

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