UROLOGICAL SURVEY   ( Download pdf )

 

INVESTIGATIVE UROLOGY

Urinary Hyaluronan as a Marker for the Presence of Residual Transitional Cell Carcinoma of the Urinary Bladder
Passerotti CC, Bonfim A, Martins JR, Dall’Oglio MF, Sampaio LO, Mendes A, Ortiz V, Srougi M, Dietrich CP, Nader HB
Disciplina de Urologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil
Eur Urol. 2006; 49: 71-5

  • Objective: The purpose of this report is to evaluate the value of urinary hyaluronan (HA) as a maker of residual transitional cell carcinoma (TCC).
  • Patients and Methods: Urine samples were collected from 83 patients hospitalized for transurethral resection (TUR). Patient ages ranged from 36 to 86 years. Samples were taken both before and after surgery. HA analysis was performed using an “ELISA-like” fluorometric assay.
  • Results: Patients were divided into two groups: a control group whose previous diagnosis was negative for tumors (n=22) and another with positive diagnosis for tumors (n=61) which was further sub-divided into with and without residual tumor. After the second procedure 47 individuals did not display residual tumor, whereas 14 (23%) did. The average HA in the control group was 8.3 microg/L pre- and 7.1 post-operatively, hence, no change occurred (p=0.471). In the group with TCC patients, the HA dropped from 885.5 microg/L to 215.3 microg/L with residual tumors and from 234.3 microg/L to 11.2 microg/L for those without residual tumor. Using a cut-off value of 20 microg/L, the sensitivity to detect residual tumor is 92.9% and specificity is 83%.
  • Conclusion: HA in addition to being one of the best markers for the initial evaluation of bladder carcinoma can be used to determine the presence of a residual tumor. This is associated with poor prognosis.

  • Editorial Comment
    This is a welcome from lab to bedside article demonstrating that the glycosaminoglycan (GAG) hyaluronan is a good marker for detecting the presence of residual transitional cell carcinoma of the bladder. In addition to traditional methods such as cystoscopy and urine cytology, hyaluronan detection is promise. Although the technique for hyaluronan analysis is being more widely used, unfortunately, it is not available yet in the majority of hospitals.
    In every study concerning GAG urinary analysis it is important to take into account some variations that we have detect in our own laboratory. When investigating whether the menstrual cycle affects urinary GAG excretion in normal young women, we found a significant increase in total urinary GAG excretion in the first half of the cycle, which paralleled the normal increase in serum estrogen levels that occurs at this phase (1). In general, estrogen inhibits the synthesis of extracellular matrix molecules by many mesenchymal cell types, such as vascular smooth muscle cells. Such inhibition would shift normal proteoglycan turnover toward degradation, which could explain the increase in GAG urinary excretion that was found in the first half of the cycle. It was not observed significant variation in the relative concentration of sulfated GAG during the different phases of the cycle. On the other hand, our results indicate that heparan sulfate was the prevailing urinary GAG during the whole cycle. Because heparan sulfate is the most abundant GAG in the glomerulus, the present findings support the hypothesis that renal structures are one of the main sources of urinary GAG.
    Since these previous results (1) indicate that urinary GAG excretion during the normal menstrual cycle has a significant and consistent variation, studies evaluating GAG excretion in women could lead to misleading or erroneous results if comparisons were made among samples taken from different phases of the cycle. This may be indeed the reason underlying the inconsistent results in previously published reports concerning GAG urinary excretion in various diseases, such as interstitial cystitis, lithiasis, genitourinary tumors, etc.
    The authors should be commended for that important investigative work with immediate clinical application, and for such more than welcome integration between basic science and clinical urology.

Reference
1. Maroclo MV, Pereira SD, Sampaio FJ, Cardoso LE: Urinary glycosaminoglycan excretion during the menstrual cycle in normal young women. J Urol. 2005; 173: 1789-92.

Dr. Francisco Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil