TRANSITIONAL CELL-CARCINOMA OF THE RENAL PELVIS AND URETER - PROGNOSTIC RELEVANCE OF NUCLEAR DEOXYRIBONUCLEIC-ACID PLOIDY STUDIED BY SLIDE CYTOMETRY - AN 8-YEAR SURVIVAL-TIME STUDY

In 72 patients with urothelial carcinoma of the renal pelvis or ureter 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). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) 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 histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis.