TMPRSS2-ERG fusion transcripts expression in patients referred for prostate biopsy: combining detection in urine and needle rinse material.

OBJECTIVES: The objective of this study was to combine urine and prostate biopsy rinse material (BRM) assays to increase sensitivity for fusion gene detection. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Interleukin-10 promoter (-1082) polymorphism in association with repeated hospital-acquired infections in elderly patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our data support a determinant role for interleukin-10 (-1082) polymorphism in the development of nosocomial infections.

TMPRSS2-ERG fusion transcripts in matched urine and needle rinse material after biopsy for the detection of prostate cancer.

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.