Detection of Core2 ß-1,6-N-Acetylglucosaminyltransferase in Post-Digital Rectal Examination Urine Is a Reliable Indicator for Extracapsular Extension of Prostate Cancer.

To identify appropriate candidates for aggressive treatment such as radical prostatectomy or radiation therapy of localized prostate cancer (PCa), novel predictive biomarkers of PCa aggressiveness are essential. Core2 ß-1,6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2-branched O-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression to the clinicopathological status of PCa. Paraffin-embedded PCa specimens were analyzed by immunohistochemistry for GCNT1 expression using a newly established mouse anti-GCNT1 mAb by ourselves. GCNT1-positive tumor showed significantly higher Gleason score and larger tumor volume. The number of GCNT1-positive cases was significantly lower in cases of organ-confined disease than in cases of extracapsular extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that detection of GCNT1 expression was an independent risk factor for PSA recurrence. We established new methods for GCNT1 detection from PCa specimens. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of PSA showed extracapsular extension. In conclusion, GCNT1 expression closely associates with the aggressive potential of PCa. Further research aims to develop GCNT1 detection in post-DRE urine as a marker for PCa aggressiveness.

[Significance of urinary biomarkers in differential diagnosis of acute tubulointerstitial nephritis].

OBJECTIVE: To find some urinary biomarkers with significance in the differentiation of drug-induced tubulointerstitial nephritis (DTIN). METHODS: Forty patients with biopsy-proven DTIN were enrolled. The urine samples of DTIN patients were collected on the day of biopsy and all urine samples were measured for the following different biomarkers as indicated, respectively: urinary TGF-beta by ELISA; urinary IL-6 by radio-immunoassay; NAG by an enzyme-substrate colorimetric assay; alpha1-MG by immune transmission turbidity method. Receiver operating characteristic curves (ROC curve) were constructed to calculate the sensitivity and specificity of those biomarkers in distinguishing acute (A-DTIN) and chronic DTIN (C-DTIN). RESULTS: Urinary NAG and alpha1-MG levels in patients with A-DTIN were as 2.5 and 2.1 times as those in C-DTIN (P<0.05), while urinary TGF-beta levels in the two groups had no statistical difference. The areas under ROC curve (AUC) of urinary NAG and alpha1-MG for differentiating A-DTIN were 0.720 (P=0.029) and 0.714 (P=0.034) respectively, while the AUCs for TGF-beta and IL-6 were 0.536 (P=0.767) and 0.150 (P=0.004) respectively. Combined measurement of NAG and alpha1-MG could make sensitivity and specificity reach 78.6% and 75.0 % respectively. CONCLUSION: Urinary alpha1-MG and NAG levels can reflect the acute lesions of DTIN, and combined measurement of both could enhance efficiency in differentiating A-DTIN.

Study of renal metabolic disturbances related to renal lithiasis at school age in very-low-birth-weight children.

We studied 34 asymptomatic children who were born with a very-low-birth-weight (VLBW) and had no perinatal history of acute renal failure nor treatment with furosemide. The study was done at preschool or school age, looking for echographic changes and renal tubular disturbances which are known to predispose to renal lithiasis. The results were compared with those of a control group of 18 children who had been born at term with a body weight >2,500 g. One or more renal tubular disturbances were found in 64.70% of the VLBW children. Most frequently found were decreased ammonium excretion in response to furosemide (38.23%), enhanced N-acetylglucosaminidase excretion (35.29%), hypercalciuria (26.47%), and hypocitraturia (23.53%). Echography revealed renal cortical hyperechogenicity (17.65%) and renal lithiasis (8.82 %) in some of the VLBW children. We found a significant positive correlation (r = 0.7) between the perinatal level of plasma phosphate and the total amount of H+ excreted in response to furosemide at preschool or school age. Because these renal tubular anomalies may be precursors of future lithiasis, and the renal function and echography tests are not invasive, we suggest that renal tubular function be measured and followed up in every VLBW child, particularly when perinatal hypophosphatemia has occurred.