473 DIFFERENTIAL GENE EXPRESSION PROFILING IN PROLIFERATIVE INFLAMMATORY ATROPHIA COMPARED TO PROSTATE CARCINOMA AND HIGH GRADE PROSTATIC INTRANEOPLASIA USING FROZEN MICRODISSECTED TISSUES

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2012473 DIFFERENTIAL GENE EXPRESSION PROFILING IN PROLIFERATIVE INFLAMMATORY ATROPHIA COMPARED TO PROSTATE CARCINOMA AND HIGH GRADE PROSTATIC INTRANEOPLASIA USING FROZEN MICRODISSECTED TISSUES Maria T. Quiles, Maria A. Arbós, Ines de Torres, Carmen Blázquez, Jaume Reventós, and Juan Morote Maria T. QuilesMaria T. Quiles Barcelona, Spain More articles by this author , Maria A. ArbósMaria A. Arbós Barcelona, Spain More articles by this author , Ines de TorresInes de Torres Barcelona, Spain More articles by this author , Carmen BlázquezCarmen Blázquez Barcelona, Spain More articles by this author , Jaume ReventósJaume Reventós Barcelona, Spain More articles by this author , and Juan MoroteJuan Morote Barcelona, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.542AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Relevance of proliferative inflammatory atrophia (PIA) as a premalignant lesion in prostate cancer remains uncertain. To elucidate the relationship between both kinds of lesion we tried to characterize signalling pathways in PIA and compared them with high grade prostatic intraneoplasia (HGPIN) and cancer (CA). METHODS Prostatectomy specimens (n=20) were collected from Oct 2007 to July 2009. Mapped tissue blocks from medial transverse sections were sectioned into two mirror blocks to be either frozen or formalin-fixed and paraffin embedded. Paired representative areas of benign prostatic tissue, HGPIN, PIA and CA (Gleason grade 6-9) were selected. Corresponding frozen blocks were serially cut and stained (Arcturus staining kit). Lesions were isolated using LCM microscopy and total RNA was extracted. After RNA amplification (Nugen Technology) transcriptional profiling was performed with Affymetrix human U133 plus 2.0 arrays. Genes showing log fold-change >1,5 in expression level between lesions (CA, HGPIN and PIA) and benign tissues were identified as differentially expressed (FDR < 1%). Enrichment analysis was performed using DAVID Bioinformatics. Ten transcripts were reverified by qPCR. AGR2 protein expression was evaluated by immunohistochemistry (H-score method). RESULTS Transcriptional profiling yielded a PIA-specific signature (379 transcripts) associated to inflammation, apoptosis, angiogenesis and cell adhesion. Similarly, HGPIN and CA gene signatures were established (68 and 426 transcripts). Transcriptional program shared by PIA and CA was significantly enriched in processes linked to positive regulation of apoptosis and steroid biosynthesis. Differentially expressed genes common to both HGPIN and CA were highly enriched in transcription and translation-associated processes, as well as cell migration. PIA, HGPIN and CA shared genes involved in extracellular matrix organization (collagens and proteoglycan metabolism-related genes). AGR2 and TMEM178 were the most highly upregulated genes. We found correlation between microarray and qPCR results. AGR2 protein was overexpressed in PIA, HGPIN and cancer compared with benign samples (p<0.001). CONCLUSIONS Our study reveals biological processes that may underlie carcinogenetic programs. Results suggest that AGR2, a known prostate cancer marker, is an early cancer biomarker in PIA lesions, which is consistent with the hypothesis that PIA is a premalignant lesion in prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e194 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maria T. Quiles Barcelona, Spain More articles by this author Maria A. Arbós Barcelona, Spain More articles by this author Ines de Torres Barcelona, Spain More articles by this author Carmen Blázquez Barcelona, Spain More articles by this author Jaume Reventós Barcelona, Spain More articles by this author Juan Morote Barcelona, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...