title: Tumor-Associated Macrophage Infiltration in Colorectal Cancer Liver Metastases is Associated With Better Outcome.
abstract: BACKGROUND
  Tumor-associated macrophages (TAMs) support growth in most human cancers, with the notable exception of colorectal adenocarcinoma, in which TAM infiltration of primary tumors is correlated with a better outcome. The importance of TAMs in colorectal liver metastases (CLM) is unknown.
  
  
  METHODS
  Using a tissue microarray of CLM resected at their institution from 1998 to 2000, the authors quantified immune marker expression by immunohistochemistry (IHC) using Metamorph Image Analysis software. Findings showed that CD68, CD3, CD4, CD8, FoxP3, and MHC-I were correlated with overall survival (OS) and disease-free survival (DFS).
  
  
  RESULTS
  Tumor cores from 158 patients were analyzed. The median follow-up period was 117 months for survivors (n = 39). The univariate analysis showed a significant positive association between DFS and CD4+(p = 0.025) and CD68+(p = 0.007). The findings showed a significant positive correlation of OS with CD4+(p = 0.042), whereas the correlation with CD68+was not significant (p = 0.17). Cutoffs were determined to dichotimize each marker for the highest log-rank statistic. Patients with CD4highhad a median OS of 115 months and DFS of 41 months (p = 0.007 compared with 40 and 16 months, respectively, for patients with CD4low(p = 0.022). Patients with CD68highhad a median OS of 50 months and a median DFS of 25 months (p = 0.67) compared with 43 and 15 months (p = 0.028). In the multivariate analysis of factors affecting DFS, high CD68 was associated with longer DFS (hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.43-0.94; p = 0.02), independently of clinicopathologic variables and CD4.
  
  
  CONCLUSIONS
  High TAM infiltration in resected CLM is associated with better outcome, independently of known clinicopathologic and immune predictors. This suggests that TAM depletion, which is being tested clinically in other cancers, may be detrimental in CLM.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cavnar
authors.affiliation: Department of Surgery, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.affiliation: Department of Surgery, Roger Williams Medical Center, Providence, RI, USA.|Department of Surgery, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuk
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Balachandran
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. dematter@mskcc.org.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate