Cell material from 100 cases of newly diagnosed bladder tumours was studied with rapid flow cytofluorometric DNA analysis. The degree of ploidy and the percentage of cells in the S-phase characterising the proliferation pattern of the tumours were determined from DNA histograms. The results were related to the tumour categories and to the histopathological grading of the tumours. Approximately 40% of T1 tumours showed aneuploid DNA patterns, while in the other categories aneuploidy was found in almost all cases. With few exceptions, tumours of Grade 1 were found to be diploid and tumours of Grade 3 aneuploid. In tumours of Grade 2, two-thirds were found to be diploid and one-third aneuploid. In the group of aneuploid tumours the tetraploid cases exhibited the least malignant characteristics as judged by histological grades and tumour categories. The aneuploid non-tetraploid tumours increased in malignancy the more they deviated from tetraploidy. This might be explained by our observations of a positive correlation between the degree of ploidy and the degree of proliferation. The proliferation increased from 10% in tetraploid tumours to 20% in triploid and pentaploid tumours.

229 patients with Grade 1-2 tumours (WHO), all category Ta or T1 (UICC) and surgically treated, were followed clinically and by flowcytofluorometric DNA-analysis (FCM). The tumours were characterised by their DNA profile. 175 cases were found to be diploid and fifty-four cases showed aneuploidy. The mean follow-up time with continuous FCM analysis was 2.6 years. During this period 19 patients showed tumour progression and 11 of these patients died. No progressive cases were found among 175 patients with repeatedly diploid DNA patterns. Thus tumour progression was exclusively linked to an aneuploid DNA pattern. In these case the degree of ploidy determined the frequency of progression: while 50% of the cases with triploid--hypotetraploid DNA pattern showed progression, only 10% of tumours with a tetraploid amount of DNA were found to be progressive. The degree of ploidy in 33 cases with recurrent aneuploid tumours was in general found to be constant. A fairly high degree of consistency was also found in the number of cells in S-phase, expressing proliferative properties. This indicates that superficial bladder tumours can be well characterised by their DNA profiles, that is the degree of ploidy and the proliferation pattern.

Biopsies from bladder tumors of 41 patients were investigated by flow-cytofluorometric DNA analysis and compared with exfoliated cells. The degrees of ploidy and proliferation were determined. Good agreement was found between the degrees of ploidy and proliferation in the biopsies and the exfoliated cell material. Tumors Grade I-II were either euploid or aneuploid. All Grade III tumors were aneuploid. The S-phase fractions were about 6% in the diploid tumors and 17% with large variations in the aneuploid tumors. The histological grading was well correlated to the number of S-phase cells and the occurrence of aneuploidy. When the Grade II tumors were divided into two groups having lesser and more pronounced atypia, the two groups differed significantly with regard to their degrees of proliferation. In addition to aneuploidy as an important criterium for malignancy, the degree of proliferation appears to be of major biological significance.

A grading system was applied in a retrospective study of 124 patients with transitional cell carcinoma of the bladder using a modified Bergkvist system. The intermediate World Health Organization (WHO) grade II tumors were divided into supposedly benign and malignant forms of grades IIa and IIb, respectively. The 5-year survival was 92% for patients with grade IIa urothelial carcinoma, compared to 43% for patients with grade IIb tumors. The corresponding figures for grades I and III tumors were 100 and 44%, respectively. When excluding carcinoma in situ (5-year survival 50%) no patient with a noninvasive tumor (stage Ta) died of bladder carcinoma within 5 years, compared to 50% of those with invasive cancers (stages T1 to T4). We propose a new grading system in which grades I and IIa are embraced as grade A, grades IIb and III as grade B, and grade IV as grade C. The 5-year survival rate in the 3 grades was 94, 44 and 27%, respectively. Grade A seems to represent a type of tumor with universally favorable prognosis, in contrast to grades B and C. This offers practical advantages, since the former can be treated conservatively, whereas the latter need more urgent radical intervention, especially in patients in whom invasive growth is recorded.