PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

Abstract

Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy). Experimental Design: PTOV1expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. Fifty patients with HG-PIN without concomitant cancer at their first prostate needle biopsy were chosen as the study group. Patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39). Results: PTOV1expression in HG-PIN from radical prostatectomies showed a significantly higher Histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). In the study group, PTOV1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22%) compared with samples in which cancer was not detected (151.4 versus 94.6). PTOV1expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95% confidence interval, 0.728-0.878). A threshold of 100 for PTOV1 expression provided 90.9% sensitivity, 51.3% specificity, 34.5% positive predictive value, and 95.2% negative predictive value. Conclusions: PTOV1 is overexpressed in HG-PIN associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. Prostate needle biopsy with PTOV1 expression in HG-PIN above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.Prostate tumor overexpressed-1 (PTOV1) was identified in our laboratory as a novel gene and protein during a screening for genes differentially expressed in prostate cancer. PTOV1 protein consists of two repeated blocks of 151 and 147 amino acids, joined by a short linker peptide, and is encoded by a 12-exon gene localized in chromosome 19q13.3 (1). The expression of PTOV1 is regulated by androgens (2). By immunohistochemical analysis, PTOV1 was undetectable in normal prostate tissue and benign prostate hyperplasia, whereas a strong immunoreactivity was shown in areas of carcinoma and high-grade prostatic intraepithelial neoplasia (HG-PIN). The high expression of PTOV1 in tumors correlated with their proliferative status, assessed by Ki67 immunoreactivity, and associated with nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In cultured prostate tumor cells, PTOV1 localized in the cytoplasm of quiescent cells and after serum stimulation, the protein partially translocated to the nucleus. Exogenous overexpression of tagged-PTOV1 induced the entry of cells into the S phase of the cell ...

Is There a Role for Prostate Tumour Overexpressed-1 in the Diagnosis of HGPIN and of Prostatic Adenocarcinoma? A Comparison with α-Methylacyl CoA Racemase

“…The protein PTOVI is overexpressed in 71% and 80% of pea and HGPIN cases, respectively, while it is expressed at low levels in normal prostate epithelium (3,5). PTOVI is expressed at high levels in neuroendocrine cells and in endothelial cells (9).…”

Chemopreventive Target for Prostate Cancer: Prostatic Intraepithelial Neoplasia

“…Select anti-keratin antibodies such as 34 -E12 (high molecular weight keratin) may be used to stain tissue sections for the presence of basal cells, recognizing that PIN retains intact or fragmented basal cell layer, whereas cancer does not (Bostwick and Brawer, 1987). By immunohistochemical analysis, Prostate tumor overexpressed-1 (PTOV1) was considered as good marker for PIN which shows strong immunoreactivity in areas of carcinoma and HGPIN (Morote et al, 2008) …”

Premalignant and Malignant Prostate Lesions: Pathologic Review

“…HGPIN adjacent to carcinoma is reported to show significantly more AMACR expression (56%) than HGPIN distant from carcinoma (14%). [57][58][59] Patients with any HGPIN gland that is AMACR-positive are 5.2 times more likely to show carcinoma on repeat biopsy than those with completely AMACR-negative HGPIN. [57][58][59] Further studies are needed to determine the utility of AMACR and PTOV1 gene in identifying which patients with HGPIN are at greater risk for carcinoma.…”