title: Elevated levels of proliferating and recently migrated tumor-associated macrophages confer increased aggressiveness and worse outcomes in breast cancer.
abstract: OBJECTIVE
  Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumor-associated macrophages (PCNA(+) TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA(+) TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA(+) TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types.
  
  
  METHODS
  We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA(+) TAM counts and were correlated with patient outcomes adjusting for HR status and histologic grade.
  
  
  RESULTS
  Like PCNA(+) TAMs, high Mac387 counts were associated with HR negativity, high tumor grade, younger age, and decreased recurrence-free survival. Mac387, however, appears to identify both a subset of macrophages and a subset of tumor cells. The concordance between Mac387 and PCNA(+) TAM counts was low and cases that had both high Mac387 and high PCNA(+) TAMs counts had a stronger association with early recurrence.
  
  
  CONCLUSIONS
  The presence of high numbers of PCNA(+) TAMs and Mac387-positive cells in breast cancers with poor outcomes may implicate a subset of TAMs in breast cancer pathogenesis, and may ultimately serve to develop potential cellular targets for therapeutic interventions.
authors.affiliation: Department of Surgery, University of California, San Francisco, CA, USA.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Mukhtar
authors.forename: Amy P
authors.initials: AP
authors.lastname: Moore
authors.forename: Vickram J
authors.initials: VJ
authors.lastname: Tandon
authors.forename: Onouwem
authors.initials: O
authors.lastname: Nseyo
authors.forename: Patrick
authors.initials: P
authors.lastname: Twomey
authors.forename: Charles Adeyinka
authors.initials: CA
authors.lastname: Adisa
authors.forename: Ndukauba
authors.initials: N
authors.lastname: Eleweke
authors.forename: Alfred
authors.initials: A
authors.lastname: Au
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.forename: Dan H
authors.initials: DH
authors.lastname: Moore
authors.forename: Michael S
authors.initials: MS
authors.lastname: McGrath
authors.forename: Olofunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campbell
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D040501:Calgranulin A; D040502:Calgranulin B; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone