Abstract
Prostate cancer in Indonesia is the 3rd ranking cancer among males and the 5th rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.
Highlights
Prostate cancer in Indonesia is the 3rd ranking cancer among males and the 5th rank for their cancer mortality
All BPH specimens had
High frequency of ALDH1A1 expression had been found in ovarian cancer, in which 28.9% tumors had 21-100% staining and 44% tumors had 1-20% staining (Landen et al, 2010)
Summary
Prostate cancer is the second most frequently diagnosed cancer of men (899.000 new cases, 13.6% of the total) and the fifth most common cancer overall. In clinical study, the high ALDH1 expression in prostate cancer was positively correlated with Gleason score and pathologic stage, and inversely associated with overall survival and cancer-specific survival of the patients (Li et al, 2010) How these prostate cancer stem cells are being initiated? The expression of cytoplasmic p63 and ALDH1 between epithelium of PIN and prostate cancer in different histological grade will be compared in order to give us insight into prostate cancer initiation and progression by a subset of cancer stem cells Their association with cell kinetics (cell proliferation and apoptosis) will be investigated. These specific markers could be developed as a new diagnostic system for early detection and prognostic determination in progression of prostate cancer, and probably offering a target therapy to cure the challenging malignancy
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