Improved objectivity of grading of T-A,(1) transitional cell carcinomas ofthe urinary bladder by quantitative nuclear and proliferation related features

Aim-To analyse whether the mean nuclear area of the 10 largest nuclei (MNA- 10), the mitotic activity index (MAI), and Ki-67 immunoquantitative feature s have additional value to discriminate different grades of T-A,T-1 transit ional cell carcinoma (TCC) of the urinary bladder. Materials/Methods-One hundred and fifty of 200 consecutive cases (75%) show ing interobserver agreement on duplicate blind grade assessment by independ ent pathologists were studied. Using random numbers, the 150 cases were div ided into sets for learning (n = 75) and testing (n = 75). Single and multi variate analyses were applied to discriminate the different grades in the l earning set. The multivariate classifier developed in this way was evaluate d in the test set (n = 75). Results-With the MNA-10 alone, using the classification MNA-10 < 80 mum(2) = grade 1, 80 mum(2) < MNA-10 < 130 mum(2) = grade 2, MNA-10 > 130 mum(2) = grade 3, 71% of all 150 cases were correctly classified (69% of grade 1 v grade 2 and 76% of grade 2 v grade 3). With multivariate analysis, the best discriminating features in the learning set (17 grade 1, 30 grade 2, and 2 8 grade 3) between grades 1 and 2 were MNA-10 and MAI, and between grades 2 and 3 MAI and Ki-67. With these features, 94% of grade I v grade 2 and 97% of grade 2 v grade 3 were correctly classified in the learning set (overal l, 95% correct, none of the grade 3 cases misclassified). In the test set t he classification results were similar. When the three grades were entered at the same time for discrimination, Ki-67 area % and MAI was the best disc riminating combination, both in the sets for learning and testing. Overall correct classification results in the sets for learning and testing were sl ightly lower, but still 94% and 92%. Most importantly, none of the grade 3 cases was misclassified; the classification shifts all occurred between gra des 1 and 2. Conclusions-The combination of MNA-10, MAI, and Ki-67 gives much better dis crimination between grades 1, 2, and 3 in T-A,T-1 TCC of the urinary bladde r than MNA-10 alone. The similarity of the classification results of the le arning set and test set are encouraging and this quantitative pathological grading model should be applied in a prospective study.