Abstract
Cell proliferation of transitional cell bladder cancer (TCC) was determined by PCNA (proliferating cell nuclear antigen)/cyclin immunostaining in 178 TCCs and the results were related to established prognostic factors, progression and survival during a mean follow-up period of 10 years. The fraction of PCNA/cyclin positive nuclei was related to T-category (P = 0.008), papillary status, WHO grade, DNA ploidy, S phase fraction, M/V index (volume corrected mitotic index) and AgNORs (silver stained nucleolar organiser regions) (for all P less than 0.001). TCCs presenting with pelvic lymph node metastasis at diagnosis had a significantly higher growth fraction than the tumours confined to the bladder wall (P less than 0.001). The fraction of PCNA/cyclin positive nuclei predicted progression in T-, N- and M-categories (P less than 0.001). In Ta-T1 tumours high fraction of PCNA/cyclin positive nuclei predicted metastasis (P = 0.019). In survival analysis the fraction of PCNA/cyclin positive nuclei predicted survival in the entire cohort (P less than 0.001) and in Ta-T1 tumours (P = 0.0005). In a multivariate survival analysis the fraction of PCNA/cyclin positive nuclei showed independent predictive value in the entire cohort (P = 0.046), in papillary tumours (P = 0.006) and in Ta-T1 tumours (P = 0.015). The results show that the growth fraction as determined by PCNA/cyclin immunostaining is a significant prognostic variable in TCC.
Highlights
The fraction of nuclei positive for PCNA/cyclin varied between 0% and 100%
PCNA/cyclin immunostaining was almost entirely confined to the nucleus showing usually a diffuse uniform staining
In some of the nuclei staining was granular and in occasional cells the cytoplasm was uniformly positive for PCNA/cyclin
Summary
The study comprised patients with a newly diagnosed primary TCC treated at Kuopio University Hospital during the years 1965-1985. The follow-up analysis was done in January 1990 and the mean (s.e.) observation period is 10.2 (0.3) years (range 5-25). Occasional patients were excluded from the initial cohort (Lipponen et al, 1991b,c,d) because of insufficient biopsy specimens for immunohistochemistry. The treatment and follow-up investigators were done according to standard practice (Zingg & Wallace, 1985) and the treatment of patients has been detailed previously (Lipponen et al, 1990b, 1991b). Nodes and metastasis classification was done according to UICC 1978 (UICC, 1978) and it was based on the above mentioned examinations added with the pathologists reports. The treatment of recurrent tumours was based on the same principle as the treatment of primary tumours.
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