p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

Abstract

<br/><b>Introduction</b>: Prostate cancer in Indonesia is the 3rd ranking cancer among males and the 5th rank for theircancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and helpselect appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggestedthat stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, althoughcontroversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epitheliaincluding prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to havean oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 isassociated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostatecancer. <br/><b>Methods</b>: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embeddedtissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason scoreprostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 andALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links ofboth markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed byKruskal-Wallis test. <br/><b>Results</b>: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance ofp63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationshipswith pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was alsofound that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferatingcells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). <br/><b>Conclusion</b>: p63cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to havean important role in prostate cancer progression and may be used as molecular markers.