Abstract 433: Altered expression of lumican in prostate cancer is identified by microarray analysis

Abstract

Abstract Prostate cancer is one of the principal medical problems facing men worldwide; fortunately mortality rates from prostate cancer have been decreasing in many developed countries, as a result of improved treatments and early detection. Developing biomarkers that correlate to prostate cancer will facilitate the delivery and development of treatment therapies for patients. To accomplish this we performed a comprehensive genome-wide microarray analysis of genes differentially up- or down-regulated in PSACre;PtenloxP/loxP mutant mice and examined novel differentially expressed genes in to identify novel genes that could potentially serve as biomarkers for disease tumor characterization. Total RNAs were collected form the prostate glands of tumor bearing PSACre;PtenloxP/loxP mutant and wild type mice. cDNAs were generated and were then hybridized onto Affymetrix microarray chips and analyzed with Agilent's Gene Spring software. Microarray analysis revealed that lumican was significantly upregulated in Pten mutant mice compared to wildtype controls. qRT-PCR validation was performed and correlated to the microarray data. Immunohistochemical staining was performed on mouse prostates at various stages of the disease process. Two staining patterns were observed and tabulated, 1) prostate epithelium and 2) stroma. Mouse epithelial cell tended to stain negative in normal glands. Expression increased in moderate and poorly differentiated tumor. The highest expression patterns were observed in the prostates from castrate resistant tumors. More notable was the increased an intense staining seen in the stromal component, especially in the thickened basement membranes cancerous glands. We also examined the expression patterns of lumican in 10 cases of human prostate cancer and benign prostatic hyperplasia (BPH). Epithelial expression in human was moderate to high in benign prostatic hyperplasia, Gleason score 6, 9 and metastatic tumors and moderate in Gleason score 7 tumors. Stromal staining was low in BPH and gradually increased to moderate as the Gleason score increased and high in metastatic lesions. The staining pattern of lumican was very similar to that of vimentin in both human and mouse tissues. Our data has shown that lumican may be differentially expressed in various stages of prostate cancer, however, larger number of clinical need to be evaluated to establish a clear correlation to clinicopathological features. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 433. doi:10.1158/1538-7445.AM2011-433