AgNOR analysis and morphometry were performed on biopsies of patients with prostate carcinoma at diagnosis to test the association between AgNORs, morphometric parameters and prognosis. Needle biopsies from 47 carcinomas (3 grade 1, 33 grade 2 and 11 grade 3), fixed in formalin and embedded in paraffin, were stained with the method of Ploton and the mean AgNOR count was assessed in 100 tumor cells for each case. Nuclear and nucleolar areas were assessed in 100 cells with an automated image analyzer (Immagini & Computer, Rho, Italy). The mean age of the patients was 72.5 years (60 to 89); no prostatectomy was performed; follow-up ranged from 1 to 115 months (mean 42). Data were processed using BMDP statistical software. The mean AgNOR count for the whole series was 8.37 (median 7.78, SD 2.66) and was associated with the degree of tumor differentiation: 5.03 for G1, 7.73 for G2 and 11.07 for G3 carcinomas (p <0.0001). The mean nuclear area was 32.09 micron2 (median 32.36, SD 10.09) and was also associated with histologic grade. The mean nucleolar area was 3.6 micron2 (median 3.47, SD 0.95), but was not associated with histologic grade. A linear relationship was found between AgNOR counts and nuclear (r=0.57, p<0.001) or nucleolar area (r=0.66, p<0.001). On univariate analysis, the 5 year survival rates were 74% for cases with AgNOR/cell <7.78 vs 0% for AgNOR >7.78 (p<0.0001); 62% for cases with nucleolar area <3.47 micron2 vs 0% for nucleolar area >3.47 micron2 (p=0.0002); 58% for cases with nuclear area <32.36 micron2 vs 9% for nuclear area >32.36 micron2 (p=0.02). Histologic grade and age had no prognostic value. On multivariate analysis, AgNOR counts (p<0.001), nucleolar (p=0.02) and nuclear area (p=0.05) retained independent prognostic significance. Our results confirm that quantitative and reproducible parameters, such as nuclear and nucleolar area, and AgNOR counts, can predict survival in patients with prostate carcinoma at diagnosis. They also clearly indicate that AgNOR counts, which are associated with histologic grade and morphometry, are the most powerful prognostic factor.
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