High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer

Postgrad Med J. 2016 Dec;92(1094):707-714. doi: 10.1136/postgradmedj-2015-133531. Epub 2016 May 24.

Abstract

Aims: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker.

Methods: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves.

Results: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05).

Conclusions: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.

Keywords: Antigen Ki67; BCL2 protein; Breast; Invasive Ductal Carcinoma; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Area Under Curve
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Lymph Node Excision
  • Mastectomy
  • Mastectomy, Segmental
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Tamoxifen / therapeutic use
  • Tissue Array Analysis
  • Trastuzumab / therapeutic use
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tamoxifen
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab