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

  • Michael J. Campbell
  • Nathan Y. Tonlaar
  • Elisabeth R. Garwood
  • Dezheng Huo
  • Dan H. Moore
  • Andrey I. Khramtsov
  • Afred Au
  • Frederick Baehner
  • Yinghua Chen
  • David O. Malaka
  • Amy Lin
  • Oyinlolu O. Adeyanju
  • Shihong Li
  • Can Gong
  • Michael McGrath
  • Olufunmilayo I. Olopade
  • Laura J. Esserman
Preclinical study

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 cancer Proliferating macrophages Promac Tumor-associated macrophage Basal-like breast cancer Hormone receptor negative tumor Prognosis 

Supplementary material

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

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Michael J. Campbell
    • 1
  • Nathan Y. Tonlaar
    • 2
  • Elisabeth R. Garwood
    • 1
  • Dezheng Huo
    • 3
  • Dan H. Moore
    • 4
  • Andrey I. Khramtsov
    • 5
  • Afred Au
    • 6
  • Frederick Baehner
    • 6
  • Yinghua Chen
    • 5
  • David O. Malaka
    • 5
  • Amy Lin
    • 1
  • Oyinlolu O. Adeyanju
    • 5
  • Shihong Li
    • 7
  • Can Gong
    • 7
  • Michael McGrath
    • 8
  • Olufunmilayo I. Olopade
    • 5
  • Laura J. Esserman
    • 1
    • 9
  1. 1.Department of SurgeryUniversity of CaliforniaSan FranciscoUSA
  2. 2.Pritzker School of MedicineUniversity of ChicagoChicagoUSA
  3. 3.Department of Health StudiesUniversity of ChicagoChicagoUSA
  4. 4.Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoUSA
  5. 5.Department of MedicineUniversity of ChicagoChicagoUSA
  6. 6.Department of PathologyUniversity of CaliforniaSan FranciscoUSA
  7. 7.Department of PathologyUniversity of ChicagoChicagoUSA
  8. 8.Department of Laboratory Medicine and Medicine, San Francisco General HospitalUniversity of CaliforniaSan FranciscoUSA
  9. 9.Carol F. Buck Breast Care CenterSan FranciscoUSA

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