Elsevier

Human Pathology

Volume 30, Issue 11, November 1999, Pages 1314-1320
Human Pathology

Original contribution
Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count

https://doi.org/10.1016/S0046-8177(99)90062-XGet rights and content

Abstract

The proliferative activity is one of the most important single prognostic parameters in breast cancer diagnosis and the time-honored measure of proliferative activity, the mitotic figure count, is an integral component of most combined prognostic scores. The detection of the cell cycle-specific antigens Ki-67, and the development of anti-Ki-67 antibodies, including the paraffin-reactive antibody MIB-1, have established immunohistochemical detection of cell cycle-specific antigens as a measure of proliferative activity in breast cancer diagnosis. The current study was performed to correlate mitotic figure counts with the proliferative activity as assessed by MIB-1 immunohistochemistry, taking into consideration the interobserver reliability of 5 pathologists in estimating mitotic figure counts. In 32 consecutive invasive ductal breast carcinomas, mitotic figure counts were performed independently by 5 pathologists. Mitotic activity was expressed as number of mitotic figures per 10 high-power fields and in a 3-tier score according to the Scarff Bloom Richardson system. Immunohistochemistry was performed using MIB-1 antibody, heat-induced epitope retrieval, and the standard avidin-biotin-immunoperoxidase method. MIB-1 immunohistochemistry was assessed in 3 representative 20 × fields by semiquantitative estimation (% of tumor cells positive) and by image analysis (number of MIB-1-positive cells/mm2). We found a high degree of interobserver correlation among 4 experienced pathologists, in both mitotic figures per 10 high-power fields and the 3-tier scoring system. We observed significant, albeit weak, correlations between semiquantitative and quantitative MIB-1 immunohistochemistry and the number of mitotic figures per 10 high-power fields (r between .36 and .53), but this significance was lost in 3 of the 5 observers when mitotic activity was expressed in the 3-tier scoring system. This study confirms mitotic figure counting in the hands of experienced pathologists as a valid, reproducible means of assessing proliferative activity in routine breast cancer diagnosis. The statistically significant, albeit only weak, correlation with MIB-1 immunohistochemistry is in agreement with results obtained by others and suggests that MIB-1 immunohistochemistry cannot be translated by a simple conversion factor into combined prognostic scores to replace the time-honored mitotic figure counts.

References (42)

  • MH Galea et al.

    The Nottingham Prognostic Index in primary breast cancer

    Breast Cancer Res Treat

    (1992)
  • H Pereira et al.

    Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader?

  • HJG Bloom

    Prognosis in carcinoma of the breast

    Br J Cancer

    (1950)
  • HJG Bloom et al.

    Histological grading and prognosis in breast cancer

    Br J Cancer

    (1957)
  • CW Elston

    The assessment of histological differentiation in breast cancer

    Aust N Z J Surg

    (1984)
  • CW Elston et al.

    Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up

    Histopathology

    (1991)
  • JP Baak et al.

    The value of morphometry to classic pronosticators in breast cancer

    Cancer

    (1985)
  • van der Linden JC et al.

    Prospective evaluation of the prognostic value of morphometry in primary breast cancer patients

    J Clin Pathol

    (1987)
  • V le Doussal et al.

    Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR): An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas

    Cancer

    (1989)
  • AM Uyterlinde et al.

    Further evaluation of the prognostic value of morphometric and flow cytometric features in breast cancer patients with long follow-up

    Int J Cancer

    (1990)
  • PK Lipponen et al.

    Volume corrected mitotic index (M/V index), mitotic activity index (MAI), and histological grading in breast cancer

    Int Surg

    (1991)
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    Supported in part by the Robert Müller Foundation, Mainz, Germany.

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