Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma

Argyrophilic proteins of nucleolar organizer regions (AgNOR proteins) were stained by a modified silver staining technique. Paraffin sections from 137 cases of invasive ductal carcinoma of the breast were investigated. The nuclei and AgNOR dots were quantitatively measured by means of a semiautomatic image analysis system. Follow-up data for about 120 months (mean, 102 +/- 47) and clinical/histologic and DNA distribution parameters were available for all patients. The prognostic significance of AgNOR parameters was tested by Cox regression analysis. Four AgNOR features showed a significant univariate correlation with survival time. In multivariate analysis offering all the available parameters, one AgNOR parameter (coefficient of variation of relative AgNOR area) ranked at the third position beyond the standard deviation of DNA distribution and pTNM/staging. When considering the distant recurrence-free survival of patients, the same AgNOR feature provided significant additional prognostic information. Performing survival analysis for the prognostically defined subgroup of pTNM/stage I patients and offering all DNA and AgNOR features the same AgNOR parameter yielded the highest prognostic validity. These results show that quantitatively measured AgNORs yield prognostic factors in breast cancer.