Differential Expression of Cell Cycle Regulated and Tumor Suppressor Gene Proteins in Localised and Advanced Prostatic Adenocarcinoma
C Barrett, R Flavin, A Murphy, B Loftus, O Sheils, JJ O'Leary. Trinity College Dublin, Dublin, Ireland; Adelaide and Meath Hospital, Dublin, Ireland
Background: The spectrum of disease severity in prostate cancer is highly variable, ranging from indolent to aggressive, making prediction for individual patients difficult. Current methods used to assess the prognosis of prostate cancer at the time of diagnosis are limited. Many proteins have already been screened by immunohistochemistry in an attempt to find a reliable predictor of progressive disease. In this immunohistochemical study we evaluated and compared protein expression of a defined panel of cell cycle regulators and tumour suppressor genes in benign prostate tissue, localised and advanced prostate cancer with a view to identifying differences in protein expression that might signify a tumors propensity to clinically progress.
Design: Prostate tissue microarrays comprising 54 cases of localised prostatic adenocarcinoma (LC), 59 cases of advanced prostatic adenocarcinoma (AC) and 61 cases of benign prostatic hyperplasia (BPH) were constructed using formalin fixed paraffin embedded archival material. Protein expression of a panel of cell cycle regulators and tumour suppressor genes; i.e., mdm2, topoisomerase II alpha, p16, Rb, cyclin d1, mib1 and p53 was detected by immunohistochemical staining of the sample cohort. The TMAs were scored semiquantitatively based on intensity (0-3) and percentage of tumor cells staining (1-4). Statistical comparison between sample cohorts was performed using the Chi square test and Fisher's exact test.
Results: There was significant (p<0.01) differential expression of cyclin D1, p16, topoisomerase II alpha and Mib-1 in cases of AC relative to cases of LC. Cyclin D1, p53, retinoblastoma, topoisomerase II alpha and Mib-1 showed significantly increased expression in AC versus BPH while p16 showed significantly increased expression in LC versus BPH.
Conclusions: AC and LC have distinctive protein expression profiles relative to each other and relative to BPH, which may have a role in the pathogenesis and progression of prostate cancer. These expression profiles could be considered as new parameters that may be useful in discriminating patients at higher risk of disease progression.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 92, Wednesday Morning