title: High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor.
abstract: BACKGROUND
  Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG).
  
  
  METHODS
  A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets.
  
  
  RESULTS
  MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-.
  
  
  CONCLUSIONS
  High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.
authors.affiliation: Department of Surgery, University Hospital Basel, Switzerland. rdroeser@uhbs.ch
authors.forename: Raoul A
authors.initials: RA
authors.lastname: Droeser
authors.forename: Christian
authors.initials: C
authors.lastname: Hirt
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger-Castori
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Viehl
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Frey
authors.forename: Christian A
authors.initials: CA
authors.lastname: Nebiker
authors.forename: Raffaele
authors.initials: R
authors.lastname: Rosso
authors.forename: Markus
authors.initials: M
authors.lastname: Zuber
authors.forename: Francesca
authors.initials: F
authors.lastname: Amicarella
authors.forename: Giandomenica
authors.initials: G
authors.lastname: Iezzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000276:immunology* / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D005647:Fucosyltransferases; D058851:GPI-Linked Proteins; D016256:Lewis X Antigen; D009195:Peroxidase; D017452:Receptors, IgG; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C504120:CEACAM8 protein, human; C428200:FCGR3B protein, human; C066693:FUT4 protein, human