title: Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma.
abstract: OBJECTIVE
  We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC).
  
  
  METHODS
  The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated.
  
  
  RESULTS
  The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX < or = 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added.
  
  
  CONCLUSIONS
  The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.
authors.affiliation: Department of Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark. hajensen@rm.dk
authors.forename: Hanne Krogh
authors.initials: HK
authors.lastname: Jensen
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
authors.forename: Marianne
authors.initials: M
authors.lastname: Nordsmark
authors.forename: Finn
authors.initials: F
authors.lastname: Lundbeck
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D018959:CD57 Antigens; D016827:CD8 Antigens; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins