Deoxyribonucleic Acid Content and Survival Rates of Patients with Transitional Cell Carcinoma of the Bladder

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Abstract
In 127 patients with urothelial carcinoma of the bladder the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Patients were followed for 1 to 9 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumor and clinical course. Tumors were histologically classified as grade 1--DNA frequency peaks in the diploid range, grade 2--heterogenous DNA distribution patterns, and grade 3-73% aneuploid and 27% tetraploid DNA values. The proliferation rate of the tumor cells was statistically greater in cases of histological grades 2 and 3 malignancy than in grade 1 malignancy. There was also a positive correlation between tumor stage and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage pT1, 64% with stage pT2 and almost 85% with stage pT3 tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell lines had no metastases and no local tumor progression for up to 9 years, whereas patients with multiple aneuploid tumor cell lines suffered recurrence and local tumor progression within 6 to 36 months. On the average, the patients died of the tumors 26 months after primary diagnosis. The difference in tumor recurrence and in tumor progression between patients with aneuploid and diploid tumors was highly significant (p < 0.001). The prognosis for patients with grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy, although they exhibit the same degree of histomorphological differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive). In terms of multivariate Cox regression analysis, DNA ploidy compared with grade and tumor stage was the strongest predictor of survival.