title: Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.
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.
authors.affiliation: Department of Surgery, University of California, San Francisco, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campbell
authors.affiliation: Pritzker School of Medicine, University of Chicago, Chicago, USA.
authors.forename: Nathan Y
authors.initials: NY
authors.lastname: Tonlaar
authors.affiliation: Department of Surgery, University of California, San Francisco, USA.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Garwood
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, USA.
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Moore
authors.affiliation: Department of Medicine, University of Chicago, Chicago, USA.
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Khramtsov
authors.affiliation: Department of Pathology, University of California, San Francisco, USA.
authors.forename: Afred
authors.initials: A
authors.lastname: Au
authors.affiliation: Department of Pathology, University of California, San Francisco, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Baehner
authors.affiliation: Department of Medicine, University of Chicago, Chicago, USA.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Chicago, Chicago, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Malaka
authors.affiliation: Department of Surgery, University of California, San Francisco, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of Chicago, Chicago, USA.
authors.forename: Oyinlolu O
authors.initials: OO
authors.lastname: Adeyanju
authors.affiliation: Department of Pathology, University of Chicago, Chicago, USA.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Chicago, Chicago, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Laboratory Medicine and Medicine, San Francisco General Hospital, University of California, San Francisco, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McGrath
authors.affiliation: Department of Medicine, University of Chicago, Chicago, USA.
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.affiliation: Department of Surgery, University of California, San Francisco, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
mesh_terms: 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