Cyclin D1 overexpression lacks prognostic significance in superficial urinary bladder cancer

Abstract

The biological behaviour of urinary bladder neoplasms cannot be adequately predicted by histological criteria alone. Cyclin D1 is a cell‐cycle regulating protein known to be overexpressed in a proportion of bladder carcinomas. To evaluate the prognostic significance of cyclin D1 expression and its relationship with tumour phenotype, 392 bladder carcinomas were analysed by immunohistochemistry. Clinical follow‐up information was available in 337 patients with superficial bladder tumours (stages pTa/pT1). Cyclin D1 positivity was seen in 176 of 392 carcinomas. Cyclin D1 overexpression was strongly linked to papillary tumour growth, low stage, and low histological grade (p<0·005 each). Multivariate analysis showed that papillary tumour growth was the only parameter which was independently linked to cyclin D1 positivity. There was no significant difference in proliferative activity (Ki67 labelling index) between cyclin D1‐negative and ‐positive tumours. Cyclin D1 positivity was not linked to the risk of recurrence or tumour progression, either in pTa or in pT1 carcinomas. It is concluded that cyclin D1 positivity distinguishes a large subgroup of papillary bladder tumours, but there is no evidence of prognostic significance for increased cyclin D1 expression. Copyright © 1999 John Wiley & Sons, Ltd.

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

“…3,4 In our study, increased expression of cyclin D1 (Ն25% positive nuclei) was more frequent in low-stage and low-grade tumors, although the differences were not significant, and was not associated with increased tumor cell proliferation, as assessed by Ki67 immunostaining. These findings are in agreement with previous studies reporting that cyclin D1 overexpression is associated with low grade and low stage 9,10,12,29 -31 and is not related with the Ki67 labeling index 12,31 nor with tumor S-phase 29 in urinary bladder cancer. A lack of association between cyclin D1 expression and tumor cell proliferation has been previously reported in breast 32 and head and neck 33 cancer.…”

“…Our results are in agreement with previous studies that also found that overexpression of cyclin D1 is associated with less aggressive disease and better survival in bladder cancer patients. 29 A lack of relationship between cyclin D1 overexpression and prognosis has been reported in superficial bladder cancer by Wagner et al, 12 who considered the presence of 10% positive cells as the cutoff to define cyclin D1 overexpressing tumors. The same authors, however, recognized that the significance of their study was hampered by the heterogeneous treatment of patients, which did not allow the exclusion that cyclin D1 status could simply affect tumor responsivity to specific treatment regimens.…”

“…It is noteworthy that, although not reaching significance, cyclin D1 overexpression was generally associated with better prognosis. 12 An important problem is that in the previous studies different cutoffs have been used to distinguish cyclin D1-overexpressing tumors, which makes more difficult a comparison between them. From this point of view, it is of interest that in our present study increased expression of cyclin D1 retained an independent prognostic significance in term of disease-free interval even when analyzed as a continuous variable in the Cox regression model, with a reduction of risk ratio of about 11% for each 10-unit increase in the percentage of positive tumor cells (data not shown).…”

“…11 However, the prognostic significance of cyclin D1 expression in urinary bladder cancer has not yet been determined. 12 Evaluation of Ki67, a proliferation-related antigen, using the MIB-1 antibody has been reported to have a prognostic significance in bladder cancer. 13 Conflicting results have also been reported about the prognostic significance of DNA ploidy and the expression level of c-erbB-2, a transmembrane glycoprotein with tyrosine kinase activity, highly homologous to the epidermal growth factor receptor.…”

Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder

“…LOH analysis of sequential carcinomas from TCC patients would, therefore enable tracking of tumour suppressor gene inactivation in relation to recurrence (Bartlett et al, 1998;Wagner et al, 1999;Watters et al, 2000).…”