Quantitative assessment of bladder carcinoma by acid labile DNA assay

BACKGROUND. Effective noninvasive methods for monitoring patients with blad der carcinoma and screening for bladder carcinoma that show better performa nce than the methods currently in use would be desirable for detecting urot helial carcinoma at an early, easily treatable stage. A rapidly hydrolyzed component of nuclear DNA has been described, the increase of which has been linked to malignancy. Quantitative determination of acid labile DNA has be en applied successfully to detect other neoplasms. This study investigates the potential of this method to detect transitional cell carcinomas. METHODS. Touch imprints of transurethral resection material from 62 cases o f nonmalignant urothelium (control group including reactive changes) and 94 cases of bladder carcinoma were analyzed. The full Feulgen hydrolysis prof iles of the nonmalignant and malignant urothelial cells were compared by me asuring the staining density of the nuclei using digital image analysis aft er various hydrolysis times. Twenty cells were sampled randomly from among the cells measured for calculation of the mean optical density (MOD). The M OD of each time was used to build the hydrolysis profile of a case. RESULTS. A hydrolysis time of 10 minutes was found to be the most discrimin ative between control and carcinoma cases. Applying a single threshold MOD Value of 101 resulted in a test sensitivity of 95.7%, a specificity of 94.4 %, a positive predictive value of 98.3%, a negative predictive value of 95. 9%, and an area under the receiver operating characteristic curve of 0.97. CONCLUSIONS. The results of this pilot study suggest that measurement of th e rapidly hydrolyzed component of DNA present in the nuclei of bladder urot helium offers a highly sensitive and reliable supplement to the qualitative and subjective cytologic procedures currently in use. Cancer 1999;86:105-1 3. (C) 1999 American Cancer Society.