ROLE OF URINARY HYALURONATE ASSAYS IN THE DETECTION OF BLADDER CARCINOMA

II. Hyaluronuria in Patients with Bladder Carcinoma

Abstract

It has been known for years that normal urothelial cells display a surface mutinous coat which is rich in acidic glycosaminoglycans such as hyaluronate. Normally hyaluronate occurs in trace levels in human urine, but it might be elevated in urine of patients with urothelial carcinomas of the bladder. A hyaluronate-specific radioassay is now in use for the determination of hyaluronate in body fluids. This assay system allows one to measure the hyaluronate concentration in the urine without any pretreatment of samples.
To test the role and usefullness of urinary hyaluranate determination in the diagnosis of bladder carcinoma, a retrospective study was performed. Twenty-four-hour urine was collected under the presence of thymol from 19 healthy subjects, 23 patients with newly-diagnosed bladder carcinoma, 11 patients with urolithiasis and 6 patients with renal cell carcinoma. Urinary excretion of total acidic glycosaminoglycans (GAG) was measured in cetylpiridinium chloride-precipitates by the carbazole reaction reported by Bitter & Muir and experssed as the amount of uronic acid. In normal subjects, total daily GAG excreted in the urine averaged 9.2±0.8mg (mean±S. E. M.) and the amount of hyaluronate excretion was 460±60μg/day (mean±S. E. M.). The upper limit for hyaluronate excretion was 900μg/day (mean+2S. D.) and those who excreted hyaluronate more than this normal limit were determined to have significant “hyaluronuria”.
In patients with urolithiasis, the mean value for total GAG excretion was significantly higher than that of normal subjects (p<0.05), but there was none who presented significant “hyaluronuria”. The mean levels of total urinary GAG and hyaluronate in patients with renal cell carcinoma did not differ significantly from those in healthy subjects. In those with bladder carcinoma, both the levels of total GAG and hyaluronate in the urine (13.3±1.2mg/day and 880±120μg/day, respectively) were significantly higher than in healthy subjects (p<0.05).
Out of 23 patients with bladder carcinoma, 16 had grade II or III high grade carcinomas. In these patients with high grade tumors, the hyaluronate excretion was higher as compared to those with low grade bladder lesions. In these 16 patients, 11 presented significant “hyaluronuria” (68.8%). Even in patients with low stage bladder lesions, those who had significant “hyaluronuria” seemed to have higher recurrence rate than those without it.
The significant hyaluronate in the urine of these patients seemed specific for bladder carcinoma, because this special GAG fraction decreased to normal range after successful resection of the bladder lesions. From these observations, it is concluded that the measurement of hyaluronate in the urine is valuable aids not only to diagnose but also to monitor the progression of bladder carcinoma.