New insight into Ki67 expression at the invasive front in breast cancer

PLoS One. 2013;8(1):e54912. doi: 10.1371/journal.pone.0054912. Epub 2013 Jan 31.

Abstract

Purpose: To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis.

Materials and methods: Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells' location. Subsequently, clinical-pathological parameters and prognosis were determined.

Results: In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67- cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67- cases (P = 0.001). No differences were observed between diffuse type or Ki67- cases (P = 0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05). Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001). In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001).

Conclusion: The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis

Substances

  • Ki-67 Antigen

Grants and funding

This study was funded by the China National Natural Science Foundation (No. 81102029 and 81172047). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.