Ferronika Paranita, Triningsih F X Ediati, Ghozali Ahmad, Moeljono Abraham, Rahmayanti Siti, Shadrina Arifah Nur, Naim Awang Emir, Wudexi Ivan, Arnurisa Alfa Monica, Nanwani Sandeep Tarman, Harijadi Ahmad
Department of Pathology, Faculty of Medicine, Gadjah Mada University, Indonesia.
Asian Pac J Cancer Prev. 2012;13(5):1943-8. doi: 10.7314/apjcp.2012.13.5.1943.
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.
在印度尼西亚，前列腺癌是男性中排名第三的癌症，在癌症死亡率中位列第五。因此，迫切需要能够在早期识别侵袭性前列腺癌并有助于选择合适治疗方法以最终降低死亡率的预后标志物。尽管仍存在争议，但已有研究表明前列腺中的干细胞在癌症的发生、发展和转移中发挥作用。包括前列腺在内的几种上皮组织中正常干细胞或储备细胞群体的维持已被证明受p63调控，并且p63表达的改变被认为在前列腺癌中具有致癌作用。我们假设p63的细胞质异常表达与作为癌症干细胞标志物的高ALDH1A1表达相关，从而导致前列腺癌的进展。
在两年（2009 - 2010年）期间进行横断面研究，使用免疫组织化学对79例良性前列腺增生、前列腺上皮内瘤变（PIN）、低和高Gleason评分前列腺癌的石蜡包埋组织进行研究。使用SPSS 15.0通过卡方检验分析细胞质p63与ALDH1A1之间的关联以及与病理诊断的关联。还通过Kruskal - Wallis检验分析这两种标志物与细胞增殖率（KI - 67）和凋亡率（裂解的半胱天冬酶3）的联系。
诊断时患者的平均年龄为70.0岁。p63的细胞质异常与ALDH1A1表达相关（p<0.001），并且两者均与病理诊断（包括Gleason评分）有显著关系（分别为p = 0.006和p<0.001）。此外，还发现前列腺癌中较高水平的细胞质p63与增殖细胞和凋亡细胞的频率显著相关（分别为p = 0.001和p = 0.016）。
p63细胞质异常与高ALDH1A1表达相关。这些成分被认为在前列腺癌进展中起重要作用，并且可能用作分子标志物。
