Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma. Comparison with classifications and prognosis

The relevance of silver-stained NORs for classifications and prognosis was investigated in breast tissue. Paraffin sections from 137 cases of invasive ductal breast carcinomas and 12 cases with non-tumorous ductus epithelium as controls were stained according to a modified technique and analysed. From the cancer cases follow-up data up to 10 years (45 to 165 months) and in addition clinical, histological and several DNA distribution parameters were available. The nuclei and the silver grains were measured by means of a semiautomatic image analysis system. Significant differences in AgNOR features were found between controls and diploid tumors (p < or = 0.001), diploid and aneuploid tumors (p < or = 0.001), Bloom-Richardson-gradings I, II, and III (p < or = 0.001), and between the tumor cells from patients developing metastases within 5 years and those without (p < or = 0.002). The prognostic significance of AgNORs was estimated using Cox regression analysis. Four AgNOR features were correlated significantly with survival time. In a multivariate approach offering all parameters available an AgNOR parameter (CV of relative area AgNORs) ranked at the third position beyond the SD of DNA distribution and pTNM-staging. Considering the metastases-free interval of patients the same AgNOR feature showed an independent prognostic validity.