Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.
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.
Campbell
Michael J
MJ
Department of Surgery, University of California, San Francisco, USA.
Tonlaar
Nathan Y
NY
Pritzker School of Medicine, University of Chicago, Chicago, USA.
Garwood
Elisabeth R
ER
Department of Surgery, University of California, San Francisco, USA.
Huo
Dezheng
D
Department of Health Studies, University of Chicago, Chicago, USA.
Moore
Dan H
DH
Department of Epidemiology and Biostatistics, University of California, San Francisco, USA.
Khramtsov
Andrey I
AI
Department of Medicine, University of Chicago, Chicago, USA.
Au
Afred
A
Department of Pathology, University of California, San Francisco, USA.
Baehner
Frederick
F
Department of Pathology, University of California, San Francisco, USA.
Chen
Yinghua
Y
Department of Medicine, University of Chicago, Chicago, USA.
Malaka
David O
DO
Department of Medicine, University of Chicago, Chicago, USA.
Lin
Amy
A
Department of Surgery, University of California, San Francisco, USA.
Adeyanju
Oyinlolu O
OO
Department of Medicine, University of Chicago, Chicago, USA.
Li
Shihong
S
Department of Pathology, University of Chicago, Chicago, USA.
Gong
Can
C
Department of Pathology, University of Chicago, Chicago, USA.
McGrath
Michael
M
Department of Laboratory Medicine and Medicine, San Francisco General Hospital, University of California, San Francisco, USA.
Olopade
Olufunmilayo I
OI
Department of Medicine, University of Chicago, Chicago, USA.
Esserman
Laura J
LJ
Department of Surgery, University of California, San Francisco, USA.
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis