p63 cytoplasmic aberrance is associated with high prostate cancer stem cell expression.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Pathology, Faculty of Medicine, Gadjah Mada University, Indonesia. paranita_ferronika@yahoo.com
Paranita
P
Ferronika
F X Ediati
FX
Triningsih
Ahmad
A
Ghozali
Abraham
A
Moeljono
Siti
S
Rahmayanti
Arifah Nur
AN
Shadrina
Awang Emir
AE
Naim
Ivan
I
Wudexi
Alfa Monica
AM
Arnurisa
Sandeep Tarman
ST
Nanwani
Ahmad
A
Harijadi
D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050697:Retinal Dehydrogenase; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase