Virchows Archiv

, Volume 438, Issue 5, pp 478–484

Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment

  • Stefan Biesterfeld
  • Faraneh Farokhzad
  • Dominik Klüppel
  • Susanne Schneider
  • Peter Hufnagl
Original Article

DOI: 10.1007/s004280000351

Cite this article as:
Biesterfeld, S., Farokhzad, F., Klüppel, D. et al. Virchows Arch (2001) 438: 478. doi:10.1007/s004280000351

Abstract.

Recently, it was stated that the proliferative activity (P) of a cell population could be indirectly calculated by multiplying the MIB-1 immunopositivity and silver-stainable nucleolar organizer region (AgNOR) features extracted exclusively in MIB-1 positive (pos.) nuclei: P=MIB-1×AgNORMIB-1pos.. To study the prognostic significance of this hypothesis, MIB-1 immunohistochemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MIB-1mean) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis system AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chosen tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR countMIB-1pos., AgNOR areaMIB-1pos.). AgNOR count and AgNOR countMIB-1pos. showed a different data distribution [2.7±0.7 (mean±SD) vs 3.9±1.1; r=0.315, P=0.014]. Similar results were obtained for AgNOR area and AgNOR areaMIB-1pos. (5.1±2.1 µm2 vs 7.5±2.4 µm2; r=0.501, P<0.001). Kaplan–Meier survival curves revealed significant differences for MIB-1mean (P=0.0018) and AgNOR areaMIB-1pos. (P=0.0340). In Cox models, both parameters provided independent prognostic information. Using their combination, the P, three groups of patients with statistically different survival could be separated (P=0.0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measurements in MIB-1 positive nuclei appears to be more useful in breast cancer prognosis than the exclusive application of one of the two methods. By this combined application, probably effects of tumor biology are represented more precisely.

AgNOR MIB-1 Image cytometry Breast cancer Survival analysis

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Stefan Biesterfeld
    • 1
  • Faraneh Farokhzad
    • 1
  • Dominik Klüppel
    • 1
  • Susanne Schneider
    • 1
  • Peter Hufnagl
    • 2
  1. 1.Institute of Pathology, Technical University of Aachen, Pauwelsstraße 30, 52057 Aachen, GermanyGermany
  2. 2.Institute of Pathology, Humboldt University (Charité), Berlin, GermanyGermany