Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

PLoS One. 2016 Mar 8;11(3):e0150979. doi: 10.1371/journal.pone.0150979. eCollection 2016.

Abstract

Few studies have addressed the risk of recurrence by assessing proliferation markers in lymph node metastasis from breast cancer. Here, we aimed to examine Ki-67 expression and mitotic count in lymph nodes in comparison with primary tumors. A cohort of node positive breast cancer (n = 168) was studied as a part of the prospective Norwegian Breast Cancer Screening Program (1996-2009). The percentage of Ki-67 positivity was counted per 500 tumor cells in hot-spot areas (x630). Mitotic count was conducted in the most cellular and mitotic active areas in 10 high power fields (x400). Our results showed that Ki-67 and mitotic count were significantly correlated between primary tumor and lymph nodes (Spearman`s correlation 0. 56 and 0.46, respectively) and were associated with most of the histologic features of the primary tumor. Univariate survival analysis (log-rank test) showed that high Ki-67 and mitotic count in the primary tumor and lymph node metastasis significantly predicted risk of recurrence. In multivariate analysis, mitotic count in the lymph node metastasis was an independent predictor of tumor recurrence. In conclusion, proliferation markers in lymph node metastases significantly predicted disease free survival in node positive breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Lymphatic Metastasis
  • Middle Aged
  • Mitotic Index*
  • Neoplasm Grading
  • Patient Outcome Assessment
  • Prognosis
  • Proportional Hazards Models
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen

Grants and funding

This work was partly supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250. The study was also supported by the Norwegian Cancer Society, Helse Vest RHF, and the Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen and Vestfold Hospital Research Fund.