Ploidy Disturbance of Normal-Appearing Bladder Mucosa in Patients with Urothelial Cancer: Relationship to Morphology

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Abstract
A total of 4 patients with transitional cell carcinoma of the bladder underwent complete mapping of the mucosa and tumors with combined cytologic, histologic and flow cytometric evaluation of the extent of involvement of the neoplastic process. Flow cytometric measurement of the cellular DNA content in multiple cell samples taken at cystoscopy showed similar changes in the normal mucosa as in the tumors. These changes consisted of an increased fraction of cells with S-phase DNA content in 2 patients with grades 1 and 2 tumors, and the presence of extensive aneuploidy in 2 patients with WHO grades 2 and 3 tumors. While grade 1 and some grade 2 tumors (WHO) are composed only of diploid cells, some of the grade 2 and all grade 3 tumors consist of a mixture of diploid and aneuploid populations. Such aneuploid clones could be identified in normal-appearing mucosa and, thus, be a source of new occurrences. The impression of heterogeneity in histograms from different tumors within the same bladder is assumed to be caused by a variation in the ratio between aneuploid and diploid populations (high ratio in tumor and low in normal-appearing mucosa). This phenomenon may be the reason for variation in grading based on histological studies.