Correlation of morphometry, nucleolar organizer regions, proliferating cell nuclear antigen and Ki67 antigen expression with grading and staging in urinary bladder carcinomas

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Abstract
Objective To investigate the correlation of four different indicators of proliferation — mean nuclear area (MNA) morphometry, nucleolar organizer region (NOR) count, proliferating cell nuclear antigen (PCNA) and Ki67 antigen expression — in specimens of invasive and non‐invasive urinary bladder carcinomas with the grading and staging of the tumour and to determine which indicator is most suitable for discriminating between non‐invasive and invasive carcinomas. Materials and methods Biopsies of 58 urinary bladder carcinomas of different grade and stage (38 invasive, 20 non‐invasive) and 11 carcinomata in situ were included in the study. Ten specimens of normal bladder mucosa served as controls. Analysis of indicators was performed on sequential serial paraffin sections of the same tissue, applying each test once to one of four serial sections. Results In comparison to normal bladder mucosa the values of the four indicators were significantly greater (Pin situ and in carcinomas. Values also increased from grade 1 to grade 3 carcinomas, but indicator values were similar for carcinomata in situ and grade 2 carcinomas. All indicators correlated with each other and allowed a significant discrimination between grade 1 and 2 or grade 2 and 3 carcinomas. Non‐invasive carcinomas (Ta) showed a significantly lower proliferative activity (P< 0.001) than invasive carcinomas but there were overlapping values within the invasive carcinomas (T1, T2 and T3/4). Conclusions MNA, NOR count, PCNA index and Ki67 index could be correlated with tumour grade, but not with stage, of transitional bladder carcinoma. Of the indicators studied the Ki67 antigen was the most useful in differentiating between invasive and non‐invasive carcinomas. This could be of prognostic relevance, especially for the heterogeneous group of grade 2 carcinomas.