title: Expression patterns of candidate susceptibility genes HNF1β and CtBP2 in prostate cancer: association with tumor progression.
abstract: OBJECTIVE
  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
  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: Department of Pathology, CHU-Universite de Poitiers, Poitiers, France.
authors: Celine
authors: C
authors: Debiais-Delpech
authors: Department of Pathology, CHU-Universite de Poitiers, Poitiers, France.
authors: Julie
authors: J
authors: Godet
authors: Department of Molecular Biology, Bioalternatives, Gencay, France.
authors: Nathalie
authors: N
authors: Pedretti
authors: Department of Molecular Biology, Bioalternatives, Gencay, France.
authors: François-Xavier
authors: FX
authors: Bernard
authors: Department of Urology, CHU-Universite de Poitiers, Poitiers, France.
authors: Jacques
authors: J
authors: Irani
authors: Department of Urology, Institut Mutualiste Montsouris, Paris, France.
authors: Xavier
authors: X
authors: Cathelineau
authors: Centre d'etude et de Recherche sur les Pathologies Prostatique (CeRePP), Hospital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France.
authors: Olivier
authors: O
authors: Cussenot
authors: 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.
authors: Gaelle
authors: G
authors: Fromont
mesh_terms: D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D056970:Co-Repressor Proteins; D018450:Disease Progression; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011467:Prostate / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; C496495:HNF1B protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051539:Hepatocyte Nuclear Factor 1-beta; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human
keywords: Candidate gene analysis; CtBP2; HNF1 transcription factor; Immunohistochemistry; Prostate cancer; RT-PCR