Urinary and Tissue Levels of Scatter Factor in Transitional Cell Carcinoma of Bladder

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Abstract
We previously reported increased titers of scatter factor in urine of 20 patients with transitional cell carcinoma of the bladder compared to noncancer and cancer control groups. Scatter factor was also found in bladder tumor extracts but the number of samples examined was too small for detailed analysis. We report a followup study of larger numbers of patients with transitional cell carcinoma and controls. The scatter factor content of urine samples and bladder tissue extracts was measured by enzyme-linked immunosorbent assay. Values were normalized per milligram creatinine or tissue protein. Statistical analysis was performed using the Mann-Whitney U test or, for multiple comparisons, the Kruskal-Wallis H test. Patients with transitional cell carcinoma of the bladder (52) had higher urinary scatter factor titers than did 24 normal subjects (p <0.001) or 14 with benign prostatic hypertrophy (p <0.001), 49 with prostate cancer (p <0.001) and 13 with other genitourinary tract cancers (p <0.001). Transitional cell carcinoma cases with clinicopathological evidence of disease had greater urinary scatter factor levels than those with no evidence of disease at urine sampling (p <0.01). However, patients with transitional cell carcinomas in remission still had much greater urinary scatter factors than did normal subjects (p <0.001). In contrast, patients with active prostate cancer had urinary scatter factor levels similar to those in remission. Patients with muscle invasive or high grade transitional cell carcinomas tended to have higher urinary scatter factor levels than patients with nonmuscle invasive or low grade tumors, respectively, but the differences were not significant. Greater levels of scatter factor were present in tissue extracts of muscle invasive transitional cell carcinomas than in nonmuscle invasive tumors (p <0.001) or nontumor tissue (p <0.02). Invasion was more closely related to tissue scatter factor content than tumor grade, since high grade noninvasive transitional cell carcinomas had a scatter factor content similar to that of low grade noninvasive transitional cell carcinomas. These studies suggest that scatter factor may be a marker of bladder cancer, urinary scatter factor titers tend to reflect disease activity and particularly high tissue titers of scatter factor are found in muscle invasive cancers. A larger prospective study will be necessary to determine the clinical significance of elevated scatter factor titers in transitional cell carcinoma of the bladder.