An analysis of ASPP protein expression in prostate cancer.


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Lucia Cerundolo1, Emma Morris1, Florian Fritzsche2, Stephane Larre1, George Thalmann3, Freddie Hamdy1, Xin Lu2, Richard Bryant1
1Nuffield Department of Surgical Sciences, University of Oxford,, Oxford, United Kingdom,2Ludwig Institute for Cancer Research Ltd, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom,3Department of Urology, University of Bern, Bern, Switzerland

Background

The ASPP (apoptosis-stimulating protein of p53) family of proteins co-regulate the apoptotic function of p53 function. Evidence suggests that dysregulated ASPP function may play a role in malignant transformation in numerous cancers. iASPP inhibits p53 function whereas ASPP1 and ASPP2 activate p53 We hypothesise that ASPP protein expression may be aberrant in prostate cancer.

Method

Tissue microarray sections containing over 200 prostate tissue cores from radical prostatectomy specimens with associated follow-up data were treated with monoclonal antibodies raised against ASPP proteins. The staining intensity of benign and malignant prostate epithelium was analysed.

Results

iASPP was expressed in the nucleus of prostate epithelial cells and this expression was significantly higher in malignant nuclei compared with benign. Cytoplasmic iASPP expression was predominantly absent in benign prostate epithelium but was present in prostate cancers. The increased cytoplasmic iASPP expression in grade 3 cancers was significantly associated with both metastasis formation and prostate cancer-specific death, and high cytoplasmic iASPP expression was an independent prognostic factor in high grade prostate cancer. Cytoplasmic ASPP2 expression was predominantly absent in benign prostate epithelium but present in prostate cancer. Cytoplasmic ASPP1 expression was seen in benign prostate epithelial cytoplasm and was significantly weaker within prostate cancer overall, however we observed an increase in cytoplasmic ASPP1 expression in high grade cancers and this was significantly associated with an adverse clinical outcome. In addition to these changes we observed evidence of altered subcellular localisation of ASPP proteins between benign and malignant prostate tissues.

Conclusion

Changes in ASPP protein expression during malignant prostate transformation may have clinical significance and may represent potential prognostic indicators. Altered ASPP protein expression and/or function may affect p53 function in prostate cancer and warrants further investigation.