Differential Gene Expression Profiling in Proliferative Inflammatory Atrophy: A Comparative Molecular Study between PIA, HGPIN and Prostate Cancer
Ines de Torres, Maria Teresa Quiles, Carmen Blazquez, Maria Antonia Arbos, Alejandra Navarro, Santiago Ramon y Cajal, Juan Morote. Hospital Universitari Vall d' Hebron. Universitat Autonoma de Barcelona, Barcelona, Spain; Institut de Recerca Vall d'Hebron (VHIR), Barcelona, Spain; Hospital Universitari Vall d' Hebron.., Barcelona, Spain
Background: The relevance of proliferative inflammatory atrophy (PIA) as a premalignant lesion in prostate cancer remains uncertain. To elucidate the relationship between both kind of lesions we tried to characterize new signaling pathways in PIA and compared them to high grade prostatic intraneoplasia (HGPIN) and prostate cancer (PCa).
Design: Prostatectomy fresh specimens from 35 patients undergoing radical prostatectomy were selected.In a subset of 20 cases paired representative areas of benign prostatic tissue, HGPIN,PIA and PCa (Gleason grade 6 to 9,) were obtained. The corresponding frozen blocks were serially cut and stained (Arcturus HistoGene kit).Representative areas of PIA, HGPIN and PCa were microdessected using LCM microscopy (Leica Microsystems) and total RNA was extracted (Qiagen). After RNA amplification (Nugen Technology) transcriptional profiling was performed with Affymetrix human U133 plus 2.0 arrays. Genes showing fold-change > 1,5 in expression level between lesions (CA, HGPIN and PIA) and benign tissues were identified as differentially expressed (FDR < 1%).Gene enrichment analysis was performed using DAVID Bioinformatics.
Results: Transcriptional profiling yielded a PIA-specific signature (379 genes) associated to inflammation, apoptosis, angiogenesis and cell adhesion. Similarly, HGPIN and CA gene signatures were established (68 and 426 transcripts, respectively). The transcriptional program shared by PIA and PCa was significantly enriched in biological processes linked to the positive regulation of apoptosis and to steroid biosynthesis.PIA,HGPIN and PCa shared the regulation of genes involved in extracellular matrix organization, including collagens and proteoglycan metabolism-related genes. Among them, AGR2 was one of the most highly upregulated genes.Thus AGR2 protein was overexpressed in PIA,HGPIN and PCa compared with benign samples (3-fold in HGPIN, p<0.01; 6-fold in PIA and PCa p<0.001).
Conclusions: The analysis of the genomic transcriptional profile in PIA-specific signature reveals biological processes that may be underlying carcinogenetic programs. Our preliminary results suggest that AGR2 could be an early cancer biomarker in PIA lesions, which is consistent with the hypothesis that PIA is a premalignant lesion in PCa.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 109, Wednesday Morning