QUANTITATIVE HISTOPATHOLOGY IN THE PROGNOSTIC EVALUATION OF PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE URINARY-BLADDER

Background. Morphologic grading of malignancy is considered to be of p rognostic value in patients with transitional cell carcinomas of the u rinary bladder (TCC). This qualitative approach is, however, associate d with low reproducibility. Grading of malignancy can be carried out o n a reproducible, quantitative scale. Methods. A retrospective, progno stic study of 110 patients treated for TCC in clinical Stages Ta-T4 (m edian follow-up time, 6 years) was performed, evaluating various gradi ng techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear v(v)BAR), nuclear volume fraction, estimates of nuclea r mean profile area (a(H)BAR(nuc)), nuclear profile density index (NI) , and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. Results. The T-stage and morphologic grad e of malignancy were closely cross-correlated (+0.63 < Kendall tau < 0.71, 2P < 6.7 X 10(-16)). The estimation of nuclear v(V)BAR, was high ly efficient, with more than 85% of the associated variation attributa ble to differences between tumors. A positive significant correlation between estimates of nuclear v(V)BAR and a(H)BAR(nuc) was detected (r = +0.79), whereas an inverse correlation was documented between nuclea r v(V)BAR and NI (r = -0.63). Estimates of nuclear volume fraction sho wed no correlation with nuclear v(V)BAR. Comparisons between categoric al and quantitative data revealed the following: a decrease in average d estimates of NI for tumors in advanced T-stage and malignancy grade (2P < 0.0008); and nuclear v(V)BAR, and a(H)BAR(nuc) increased on aver age, in tumors of high T-stage and malignancy grade. Estimates of MI w ere also positively correlated with the T-stage and the malignancy gra de (+0.42 < Kendall tau < +0.49). Single-factor analyses showed progno stic effect of T-stage, grade of malignancy, and, apart from nuclear v olume fraction, all quantitative histopathologic variables with regard to overall survival (2P < 0.03). None of the morphometric and stereol ogic parameters were of prognostic values with regard to recurrence-fr ee survival (2P > 0.26). Multiple hazards regression analysis (Cox mod els) revealed that clinical stage of disease was the sole independent prognostic variable. Only estimates of nuclear v(V)BAR added significa nt independent prognostic prediction with regard to recurrence-free su rvival in the 48 patients with Ta tumors (2P = 0.03). Conclusions. The results suggested that estimates of nuclear v(v)BAR are prognosticall y superior to morphologic grading of malignancy in noninvasive TCC, wh ereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC.