Cell cycle-dependent AgNOR analysis in invasive breast cancer

OBJECTIVE: To investigate to what extent analysis of silver-stained nucleolar organizer regions (AgNORs) is cell cycle dependent in breast cancer and to assess the prognostic value of an AgNOR analysis that takes into consideration the cell cycle status of tumor cells. STUDY DESIGN: In 97 cases of invasive breast carcinoma, morphometric AgNOR analysis was performed in tumor cells with immunohistochemical MIB-1 reactivity (NORcyc analysis) and in MIB-1-negative tumor cells (NORnon analysis). Additionally, conventional (NORconv) analysis without preceding MIB-1 staining was done. Findings were compared with the Nottingham prognostic index (NPI). RESULTS: In comparison to noncycling tumor cells, cycling ones exhibited significantly higher AgNOR numbers (mean values, 3.84 +/- 1.09 vs. 2.40 +/- 0.78 per nucleus), higher total AgNOR areas (5.95 +/- 3.17 vs. 5.62 +/- 3.05 micron 2, NS) and significantly lower mean AgNOR areas (2.08 +/- 1.14 vs. 2.93 +/- 1.69 micron 2). When related to NPI, correlation coefficients of NORnon analysis were higher than those of NORcyc analysis but lower than those of NORconv analysis. Among the different AgNOR parameters, total AgNOR area correlated best with NPI. CONCLUSION: Cell cycle status has a high impact on AgNOR analysis. However, the best prognostic information in breast cancer is derived from an AgNOR analysis that considers both cycling and noncycling tumor cells.