title: Further testing of morphometric grading in T(A,1) urothelial carcinomas of the urinary bladder and the additional value of p53 immunoquantitation.
abstract: OBJECTIVE
  To analyze the value for grading of a previously developed quantitative morphometric/cytometric multivariate grading model (consisting of the mean nuclear area of the 10 largest nuclei (MNA-10, mitotic activity index = MAI and Ki-67 area% = Ki-67) in two new independent test sets of urothelial carcinomas (UCs) of the urinary bladder and to evaluate the additional value of p53 area% (p53) in this model.
  
  
  METHODS
  Ki-67 immunoquantitation, morphometric MAI and MNA-10 assessments using a previously described, strict protocol and matching of the resulting morphometric grade with subjective grade in two test sets of 154 T(A,1) UCs of the bladder (consensus grade between two independent observers). Further testing of this morphometric grading model was performed in 57 cases that lacked initial interobserver agreement on grade. Single and multivariate analysis of all features (including p53) was performed.
  
  
  RESULTS
  With the previously developed morphometric/cytometric grading model, 93% (grade 1 vs. 2) and 91% (grade 2 vs. 3) of the consensus cases were correctly classified. These percentages were very similar to previous results, suggesting that the model is robust. Of the 57 cases that lacked initial interobserver agreement on grade, 53/57 (93%) were classified unambiguously as grade 1, 2 or 3 with the quantitative morphometric/ cytometric grading model. In the exploratory analysis, p53 was significant but with more overlap than the other features had. In multivariate analysis p53 did not improve the overall classification result of the original morphometric/cytometric model.
  
  
  CONCLUSIONS
  The value of MNA-10, MAI and Ki-67 for grading in T(A,1) urothelial carcinomas of the urinary bladder was confirmed. p53 Did not improve overall grading classification of this combination.
authors.affiliation: Department of Pathology, SIR Hospital, Stavanger, Norway.
authors.forename: Marco G W
authors.initials: MG
authors.lastname: Bol
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Nelly G
authors.initials: NG
authors.lastname: Breeuwsma
authors.forename: Peter C
authors.initials: PC
authors.lastname: de Bruin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology; D016002:Discriminant Analysis; D006801:Humans; D007150:Immunohistochemistry; D007620:Karyometry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D008940:Mitotic Index; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53