Celine Debiais-Delpech1, Julie Godet1, Nathalie Pedretti2, François-Xavier Bernard2, Jacques Irani3, Xavier Cathelineau4, Olivier Cussenot5, Gaelle Fromont6. 1. Department of Pathology, CHU-Universite de Poitiers, Poitiers, France. 2. Department of Molecular Biology, Bioalternatives, Gencay, France. 3. Department of Urology, CHU-Universite de Poitiers, Poitiers, France. 4. Department of Urology, Institut Mutualiste Montsouris, Paris, France. 5. Centre d'etude et de Recherche sur les Pathologies Prostatique (CeRePP), Hospital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France. 6. Department of Pathology, CHU-Universite de Poitiers, Poitiers, France; Centre d'etude et de Recherche sur les Pathologies Prostatique (CeRePP), Hospital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France. Electronic address: g.fromont@chu-poitiers.fr.
Abstract
OBJECTIVES: Genome-wide association studies have identified variants at multiple loci associated with prostate cancer (PCa) risk. Some of these loci include candidate susceptibility genes, such as MSMB, HNF1β, and C-terminal-binding protein (CtBP2). Except for MSMB, the clinicopathological significance of these genes has not been investigated. We therefore aimed to analyze their expression in PCa tissues, in relation with tumor progression and aggressiveness. METHODS AND MATERIALS: Protein expression was evaluated by immunohistochemistry on tissue microarrays containing samples from normal prostate (NL, n = 91), high-grade prostatic intraepithelial neoplasia (PIN, n = 61), clinically localized PCa (CLC, n = 434), PCa metastases (M, n = 28), and castration-resistant PCa (CRC, n = 49). Moreover, mRNA expression for each marker was assessed by quantitative real-time polymerase chain reaction, on 53 frozen samples of NL, CLC, and CRC. RESULTS: These genes were differentially expressed at the different stages of PCa natural history. MSMB expression decreased with disease development and progression. In contrast, nuclear HNF1β and CtBP2 staining significantly increased in the CRC and M groups when compared with CLC, together with the transcripts levels. In patients with CLC, HNF1β and CtBP2 nuclear expressions were strongly associated with cancer cell proliferation. After adjusting for the Gleason score and the pathological stage, none of the candidate genes was significantly predictive of recurrence after radical prostatectomy. In patients with CRC, CtBP2 nuclear staining was associated with shorter overall survival. CONCLUSIONS: The decrease of MSMB expression during tumor progression strongly supports its role as a tumor-suppressor gene. Although its functions remain to be clarified in PCa cells, HNF1β and CtBP2 are associated with cancer cell proliferation, tumor progression, and castration-resistant disease.
OBJECTIVES: Genome-wide association studies have identified variants at multiple loci associated with prostate cancer (PCa) risk. Some of these loci include candidate susceptibility genes, such as MSMB, HNF1β, and C-terminal-binding protein (CtBP2). Except for MSMB, the clinicopathological significance of these genes has not been investigated. We therefore aimed to analyze their expression in PCa tissues, in relation with tumor progression and aggressiveness. METHODS AND MATERIALS: Protein expression was evaluated by immunohistochemistry on tissue microarrays containing samples from normal prostate (NL, n = 91), high-grade prostatic intraepithelial neoplasia (PIN, n = 61), clinically localized PCa (CLC, n = 434), PCa metastases (M, n = 28), and castration-resistant PCa (CRC, n = 49). Moreover, mRNA expression for each marker was assessed by quantitative real-time polymerase chain reaction, on 53 frozen samples of NL, CLC, and CRC. RESULTS: These genes were differentially expressed at the different stages of PCa natural history. MSMB expression decreased with disease development and progression. In contrast, nuclear HNF1β and CtBP2 staining significantly increased in the CRC and M groups when compared with CLC, together with the transcripts levels. In patients with CLC, HNF1β and CtBP2 nuclear expressions were strongly associated with cancer cell proliferation. After adjusting for the Gleason score and the pathological stage, none of the candidate genes was significantly predictive of recurrence after radical prostatectomy. In patients with CRC, CtBP2 nuclear staining was associated with shorter overall survival. CONCLUSIONS: The decrease of MSMB expression during tumor progression strongly supports its role as a tumor-suppressor gene. Although its functions remain to be clarified in PCa cells, HNF1β and CtBP2 are associated with cancer cell proliferation, tumor progression, and castration-resistant disease.
Authors: Michaela Bártů; Jan Hojný; Nikola Hájková; Romana Michálková; Eva Krkavcová; Karol Simon; Vladimír Frýba; Ivana Stružinská; Kristýna Němejcová; Pavel Dundr Journal: Pathol Oncol Res Date: 2020-06-01 Impact factor: 3.201
Authors: Ahva Shahabi; Juan Pablo Lewinger; Jie Ren; Craig April; Andy E Sherrod; Joseph G Hacia; Siamak Daneshmand; Inderbir Gill; Jacek K Pinski; Jian-Bing Fan; Mariana C Stern Journal: Prostate Date: 2016-06-08 Impact factor: 4.012