Evaluation of the argyrophilic nucleolar organizer region, nuclear DNA content and mean nuclear area in transitional cell carcinoma of bladder using a quantitative image analyzer

To search for reliable parameters that reflect the biological potential of bladder cancer, the argyrophilic nucleolar organizer region (AgNOR), nuclear DNA content and mean nuclear area (MNA) were studied in paraffin-embedded materials of 75 primary transitional cell carcinomas (TCCs) using a quantitative image analyzer, and were also compared with histological findings and prognosis. The AgNOR parameters studied were the mean AgNOR count (C-AgNOR) and the percentage of cells exhibiting more than 4 AgNOR dots within nuclei (P-AgNOR), whereas the DNA parameters were the 2c deviation index (2cDI) and 5c exceeding rate (5cER). These 5 parameters significantly correlated with the histological grade (p < 0.0001, respectively). Similarly, these 5 parameters correlated with the histological stage, but the correlation was higher in 2cDI and ScER (p < 0.0001, respectively) in comparison with the AgNOR parameters and MNA. Using univariate analysis, the prognostic relevance was noted in all but P-AgNOR. The ScER value could discriminate histological grade-II tumors in relation to prognosis, whereas the remaining parameters could not. In addition, the significant difference between noninvasive and invasive tumors was noted in 2cDI and ScER (p < 0.05, respectively), but not in C-AgNOR, P-AgNOR and MNA. These results suggest that (i) 2cDI and ScER exhibit superiority over the AgNOR parameters and MNA in predicting survival, and (ii) in histological grade-II tumors, evaluation of the ScER value is most important when predicting survival as well as judging the necessity for further aggressive treatment in patients with TCCs of the bladder.