title: The prognostic value of tumor-associated macrophages in leiomyosarcoma: a single institution study.
abstract: BACKGROUND
  High numbers of tumor-associated macrophages (TAMs) have been associated with poor outcome in several solid tumors. In 2 previous studies, we showed that colony stimulating factor-1 (CSF1) is secreted by leiomyosarcoma (LMS) and that the increase in macrophages and CSF1 associated proteins are markers for poor prognosis in both gynecologic and nongynecologic LMS in a multicentered study. The purpose of this study is to evaluate the outcome of patients with LMS from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins.
  
  
  METHODS
  Patients with LMS treated at Stanford University with adequate archived tissue and clinical data were eligible for this retrospective study. Data from chart reviews included tumor site, size, grade, stage, treatment, and disease status at the time of last follow-up. The 3 CSF1 associated proteins (CD163, CD16, and cathepsin L) were evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves and univariate Cox proportional hazards models were fit to assess the association of clinical predictors as well as CSF1 associated proteins with overall survival.
  
  
  RESULTS
  A total of 52 patients diagnosed from 1983 to 2007 were evaluated. Univariate Cox proportional hazards models were fit to assess the significance of grade, size, stage, and the 3 CSF1 associated proteins in predicting OS. Grade, size, and stage were not significantly associated with survival in the full patient cohort, but grade and stage were significant predictors of survival in the gynecologic (GYN) LMS samples (P = 0.038 and P = 0.0164, respectively). Increased cathepsin L was associated with a worse outcome in GYN LMS (P = 0.049). Similar findings were seen with CD16 (P < 0.0001). In addition, CSF1 response enriched (all 3 stains positive) GYN LMS had a poor overall survival when compared with CSF1 response poor tumors (P = 0.001). These results were not seen in non-GYN LMS.
  
  
  CONCLUSIONS
  Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA, 94305, USA. kganjoo@stanford.edu
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Ganjoo
authors.forename: Daniela
authors.initials: D
authors.lastname: Witten
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Trang
authors.initials: T
authors.lastname: La
authors.forename: Rob
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jacobs
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D056668:Cathepsin L / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000401:mortality; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D012189:Retrospective Studies; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; C534281:CTSL protein, human; D056668:Cathepsin L
keywords: tumor-associated macrophages, leiomyosarcoma