Breast Cancer Research and Treatment

, Volume 128, Issue 3, pp 703–711

Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome

Authors

  • Michael J. Campbell
    • Department of SurgeryUniversity of California
  • Nathan Y. Tonlaar
    • Pritzker School of MedicineUniversity of Chicago
  • Elisabeth R. Garwood
    • Department of SurgeryUniversity of California
  • Dezheng Huo
    • Department of Health StudiesUniversity of Chicago
  • Dan H. Moore
    • Department of Epidemiology and BiostatisticsUniversity of California
  • Andrey I. Khramtsov
    • Department of MedicineUniversity of Chicago
  • Afred Au
    • Department of PathologyUniversity of California
  • Frederick Baehner
    • Department of PathologyUniversity of California
  • Yinghua Chen
    • Department of MedicineUniversity of Chicago
  • David O. Malaka
    • Department of MedicineUniversity of Chicago
  • Amy Lin
    • Department of SurgeryUniversity of California
  • Oyinlolu O. Adeyanju
    • Department of MedicineUniversity of Chicago
  • Shihong Li
    • Department of PathologyUniversity of Chicago
  • Can Gong
    • Department of PathologyUniversity of Chicago
  • Michael McGrath
    • Department of Laboratory Medicine and Medicine, San Francisco General HospitalUniversity of California
  • Olufunmilayo I. Olopade
    • Department of MedicineUniversity of Chicago
    • Department of SurgeryUniversity of California
    • Carol F. Buck Breast Care Center
Preclinical study

DOI: 10.1007/s10549-010-1154-y

Cite this article as:
Campbell, M.J., Tonlaar, N.Y., Garwood, E.R. et al. Breast Cancer Res Treat (2011) 128: 703. doi:10.1007/s10549-010-1154-y

Abstract

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages—proliferating macrophages (promacs)—with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P = 0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.

Keywords

Breast cancerProliferating macrophagesPromacTumor-associated macrophageBasal-like breast cancerHormone receptor negative tumorPrognosis

Supplementary material

10549_2010_1154_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)

Copyright information

© Springer Science+Business Media, LLC. 2010