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INTRODUCTION Nowadays, diagnostic biomarker research is oriented on a genomic characterisation of prostate cancer (PCa). This study evaluated diagnostic values of TMPRSS2-Erg fusion transcripts expression (TE) and androgen receptor variant 7 (AR-V7) on urine (tU) and biopsic rince material (tLRB) samples. MATERIALS AND METHODS TE and AR-V7 have been tested by RT-PCR and RT-qPCR on urine and biopsies' rince liquid on 372 patients referred for prostate biopsies. RESULTS Two hundred thirty-three patients (62%) were diagnosed with PCa. tU.AR-V7 was positive for 15 healthy patients (28%) and 30 patients diagnosed with PCa (37%). tLRB.AR-V7 was positive for 66 patients (42%) diagnosed with PCa. Concerning TE for patients diagnosed with PCa, tU was positive for 59 patients (54%) and tLRB for 132 (55%). TE and TE/AR-V7 combination were significantly associated with PCa (P

Nowadays, diagnostic biomarker research is oriented on a genomic characterisation of prostate cancer (PCa). This study evaluated diagnostic values of TMPRSS2-Erg fusion transcripts expression (TE) and androgen receptor variant 7 (AR-V7) on urine (tU) and biopsic rince material (tLRB) samples.TE and AR-V7 have been tested by RT-PCR and RT-qPCR on urine and biopsies' rince liquid on 372 patients referred for prostate biopsies.Two hundred thirty-three patients (62%) were diagnosed with PCa. tU.AR-V7 was positive for 15 healthy patients (28%) and 30 patients diagnosed with PCa (37%). tLRB.AR-V7 was positive for 66 patients (42%) diagnosed with PCa. Concerning TE for patients diagnosed with PCa, tU was positive for 59 patients (54%) and tLRB for 132 (55%). TE and TE/AR-V7 combination were significantly associated with PCa (P0.001), as tLRB.AR-V7 (P0.001). Sensitivity and specificity for TE/AR-V7 combination for PCa were respectively: tU.TE/AR-V7 67% and 70%, tLRB.TE/AR-V7 68.8% and 71%, and, tUtLRB.TE/AR-V7 83% and 60%. There was no benefit for AR-V7 and TE association versus TE alone when comparing AUC.AR-V7 is not specific of PCa because of detection on healthy patients. This study did not managed to show a sufficient diagnostic value for TE/AR-V7 combination on urine and biospic rince material tests.3.

The objective of this study was to combine urine and prostate biopsy rinse material (BRM) assays to increase sensitivity for fusion gene detection.A total of 194 patients with suspicion of prostate cancer were prospectively included. Urine samples were collected before or after prostate biopsy, as well as BRM. RT-qPCR was used for the detection of fusion transcripts. A microfocal cancer on biopsy was defined by a single core involved with less than 3 mm of Gleason score 3 + 3 cancer. The association between RT-qPCR and biopsy results was statistically assessed.Seven patients were excluded because of insufficient material. Cancer was detected on biopsy in 100 (53%) patients. Urine alone, BRM alone and both samples were obtained in 155, 164 and 132 patients, respectively. In patients with evidence of cancer on biopsy, a fusion transcript was detected in 63, 55 and 73% of the cases on urine alone, BRM alone and paired samples, respectively. Fusion gene detection on BRM was only associated with the amount of cancer on biopsy. Urine fusion score had a larger area under the curve than serum PSA (p = 0.002) and was significantly higher in patients with high Gleason score and significant cancer on biopsy. Assays of paired samples allowed increasing sensitivity in all subgroups of patients.TMPRSS2-ERG fusion gene detection may be performed both in the urine and BRM to increase sensitivity. However, only T-E urine score was associated with adverse pathological features.

Objectifs Le pronostic du cancer de prostate varie en fonction des caracteristiques tumorales. La presence d’un contingent neuro-endocrine est associee a un pronostic pejoratif. Nous avons montre que le calcium peut accelerer la progression tumorale et que ses effets passent par un recepteur au calcium (CaSR), associe a un mauvais pronostic. Notre objectif a alors ete de montrer l’implication du CaSR dans la differenciation neuro-endocrine. Methodes Nous avons analyse retrospectivement les liquides de rincage du pistolet a biopsies, des patients ayant beneficie de biopsies prostatiques ciblees dans notre centre entre janvier 2013 et novembre 2016. Des qPCR ont ete realisees pour rechercher l’expression du CaSR et de la synaptophysine, un des marqueurs les mieux etablis pour les cellules neuro-endocrines. Une analyse de regression logistique multivariee a ete realisee pour rechercher les facteurs associes a l’expression de CaSR et synaptophysine. En parallele nous avons analyse par qPCR l’expression de CaSR et synaptophysine sur la lignee cellulaire tumorale prostatique humaine (LNCaP) chez lesquelles nous avons induit la differenciation neuro-endocrine. Resultats Nous avons analyse les liquides de rincage de 214 patients et 164 qPCR ont pu etre realisees sur ce materiel. Sur les 164 liquides de rincages, 100 (61,3 %) correspondaient a une biopsie positive. Le CaSR etait exprime chez 52 (32 %) patients. La synaptophysine etait exprimee chez 116 (71 %) patients. Quatre-vingt-trois pour cent des patients qui exprimaient le CaSR exprimaient la synaptophysine. Chez les patients exprimant CaSR et synaptophysine, la prevalence du cancer etait de 70 %. Chez les patients n’exprimant aucun des deux marqueurs, la prevalence du cancer etait de 44,7 % (p = 0,0232). En analyse multivariee, l’expression de CaSR et synaptophysine n’etaient pas associees a la presence de cancer, ni aux caracteristiques tumorales. La differenciation neuro-endocrine des LNCaP a montre l’apparition et la co-localisation du CaSR et de la synaptophysine au niveau cellulaire. Conclusion Le CaSR a ete associe a une surmortalite dans un travail recent, mais n’est pas associe aux caracteristiques tumorales au moment du diagnostic. Le CaSR pourrait donc jouer un role tardif dans l’evolution du cancer en favorisant l’apparition d’un contingent neuro-endocrine. Le suivi de notre cohorte pourrait permettre de valider cette hypothese.

Infections are frequent complications of hospitalization, particularly in the elderly. Pro- and anti-inflammatory cytokines are essential components of the host response to pathogens and polymorphisms in their genes may contribute to inter-individual variations of the inflammatory response. The aim of this study was to investigate whether cytokine polymorphisms, separately or in combination, could be determining factors in the development of repeated nosocomial infections in elderly hospitalized patients.Tumor necrosis factor-α (-308) and (-238), interleukin-6 (-174) and (-6331), interleukin-10 (-1082) and (-592) polymorphisms were genotyped by PCR and hybridization with fluorescent-labeled probes in 245 hospitalized elderly patients (mean age 85.2 years; SD 6) and compared with those in 145 healthy adults.The distribution of genotypes did not differ between elderly patients and control subjects. The presence of the interleukin-10 A(592) or A(1082) allele was more frequent individually and after adjustment for multiple comparisons in patients who suffered from several infections (p = 0.012, odds ratio = 5.3; 95 % confidence interval = 1.2-23.1).Our data support a determinant role for interleukin-10 (-1082) polymorphism in the development of nosocomial infections.

Objectifs Developper une methode de detection combinee du variant du recepteur aux androgenes ARV7 dans les urines et le produit de rincage du pistolet a biopsie prostatique. Evaluer la prevalence de l’ARV7 dans une population soumise au depistage du cancer de la prostate. Methodes Nous avons inclus prospectivement 161 patients adresses pour biopsies de la prostate. Des prelevements urinaires ont ete realises avant et apres biopsies, de meme qu’un prelevement du liquide de rincage du pistolet a biopsies (LRB). La recherche de transcrits de ARV7 a ete effectuee par RT-qPCR. L’analyse histologique des biopsies a precise l’existence d’un cancer, et le score de Gleason. Resultats L’âge moyen (ds) etait de 65 (8,5) ans. Le PSA moyen (ds) etait de 17,3 (37,8) ng/mL. Le taux de detection biopsique etait de 60,2 %. Au total, un transcrit de ARV7 a ete detecte sur au moins un prelevement chez 45 % des hommes ayant un cancer, et 39 % des hommes sans evidence de cancer. Les taux de detection de transcrit de ARV7 etaient respectivement de 25 %, 32 %, et 50 % sur le LRB seul, les urines seules, et les 2 tests combines ( Tableau 1 ). Les taux de detection des transcrits de ARV7 n’etaient pas statistiquement associes a l’âge, au taux de PSA, a la presence de cancer ou au score de Gleason biopsique. Conclusion La prevalence d’expression du variant ARV7 est importante. Elle ne semble pas etre associee a la presence de cancer. La sensibilite de detection pourrait etre augmentee par une etude combinee des urines et du LRB.

BACKGROUND Current methods for detecting TMPRSS2-ERG fusion transcript in the urine of patients with suspected prostate cancer lack diagnostic sensitivity. We combined urine and prostate biopsy rinse material (BRM) assays to improve the fusion gene detection rate. METHODS Eighty patients with clinical and/or prostate-specific antigen suspicion of prostate cancer were prospectively included in the study. Urine samples were collected before and after prostate biopsy, and BRM was collected from the biopsy needle. We used reverse-transcription PCR (RT-PCR) for the detection of fusion transcripts. Microfocal cancer (MFC) on biopsy was defined by a single core involved with ≤3 mm of cancer with Gleason score 3 + 3. We statistically assessed the association between RT-PCR and biopsy results. RESULTS Urine alone, BRM alone, and both samples were obtained in 4, 19, and 57 patients, respectively. Three patients were excluded because of insufficient material. In the remaining 77 patients, cancer was detected on biopsy in 42 (55%). The diagnostic sensitivity of the assay for cancer detection was 62% (95% CI 47%–78%), 69% (53%–85%), and 89% (73%–99%) with BRM alone, urine alone, and paired samples, respectively. The lowest values were obtained with the urine assay in patients with MFC or Gleason score >3 + 3 cancer. Assays of paired samples provided increased diagnostic sensitivity in all subgroups of patients. CONCLUSIONS TMPRSS2-ERG fusion gene detection may be improved by performing assays in both urine and BRM. Insufficient cell numbers in urine samples and cell lysis during centrifugation may explain the low diagnostic sensitivity of the urine assay.