WDR19 Expression is Increased in Prostate Cancer Compared with Normal Cells, but Low-Intensity Expression in Cancers is Associated with Shorter Time to Biochemical Failures and Local Recurrence

• Published in: Clinical cancer research 2008-03, Vol.14 (5), p.1397-1406
• Main Authors: BIAOYANG LIN, UTLEG, Angelita G, HOOD, Leroy, KALLAND, Karl-Henning, AKSLEN, Lars A, GRAVDAL, Karsten, WHITE, James T, HALVORSEN, Ole J, WEI LU, TRUE, Lawrence D, VESSELLA, Robert, LANGE, Paul H, NELSON, Peter S
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - physiology; Gynecology. Andrology. Obstetrics; Humans; Immunoenzyme Techniques; immunohistochemistry; Male; Male genital diseases; Medical sciences; Mice; Neoplasm Recurrence, Local - pathology; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Prognosis; prostate cancer; Prostate-Specific Antigen - metabolism; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sensitivity and Specificity; Survival Rate; Time Factors; tissue microarrays; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; WD repeat; WDR19
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-1535

Purpose: Prostate cancer is the third leading cause of cancer death in the United States, following lung and colorectal cancer. We previously identified WDR19 as a prostate-specific, androgen-regulated gene. Here, we evaluate its utility as a prostate cancer tissue marker for diagnosis and prognostic evaluation. Experimental Design: Real-time quantitative PCR was done on a panel of prostate tissue isolated by laser capture microdissection. After generating antibodies against WDR19, tissue microarrays (TMA) were employed to compare WDR19 expression between normal, benign prostatic hyperplasia, and prostate cancer tissue. Results: Using microarrays and real-time quantitative PCR, we showed that WDR19 mRNA expression was increased in cancer. We further showed that WDR19 protein is localized to cytoplasmic subcellular granules and is expressed exclusively in prostate epithelia. Large-scale immunohistochemical staining using TMAs reveals a significant percentage of increase in intensely staining tissue cores in cancer tissue when compared with normal or benign prostatic hyperplastic tissue. Based on the analysis of a separate TMA for which clinical follow-up information was available, low-intensity WDR19 staining was significantly associated with decreased time to biochemical failure ( P = 0.006) and with decreased time to locoregional recurrence ( P = 0.050). Conclusions: WDR19 should be added to the list of prostate cancer tissue markers. The continued expansion of a multiple-marker panel will conceivably increase the sensitivity and specificity of prostate cancer diagnosis and prognosis.