title: The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma.
abstract: BACKGROUND
  Natural killer (NK) cells have a spontaneous cytotoxic capacity-against tumor cells. These cells represent a small proportion of human colon carcinoma-infiltrating lymphocytes. Their prognostic significance in these tumors has yet to be determined.
  
  
  METHODS
  One hundred and fifty-seven patients who each had a colectomy for large bowel adenocarcinoma were studied. No patient received adjuvant therapy. Immunohistochemical stains were performed for NK cells using the monoclonal antibody CD57. The number of NK cells was counted using a MICRON image analyzer. The total area studied for each tumor was 1 cm2. In this area, 50 intratumoral fields of 0.173 mm2 were selected. The degree of NK infiltration was classified as little (< 50 NK cells), moderate (50-150 NK cells), and extensive (> 150 NK cells). The Kaplan-Meier method was used to obtain survival figures. Multivariate analyses were performed using the Cox regression model.
  
  
  RESULTS
  At 5 years, patients with little and moderate NK infiltration showed significantly shorter survival rates (overall and disease free survival) than those with extensive infiltration (P < 0.01). Three significant factors affecting survival were selected in a stepwise fashion in increasing order as follows: TNM stage, NK infiltration, and lymphocytic infiltration. Patients with TNM Stage III disease and extensive NK infiltration showed significantly longer survival rates than those with little or moderate infiltration (P < 0.001). In these patients, multivariate analysis using the Cox regression model identified two significant variables: number of involved lymph nodes and NK cells infiltration.
  
  
  CONCLUSIONS
  In patients with colorectal carcinoma, an extensive intratumoral infiltration of NK cells is associated with a favorable tumor outcome. Intratumoral infiltration of NK cells can be used as a variable with prognostic value, especially in patients with TNM Stage III disease.
authors.affiliation: Department of Pathology, Air Forces Hospital, Complutense University, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Coca
authors.forename: J
authors.initials: J
authors.lastname: Perez-Piqueras
authors.forename: D
authors.initials: D
authors.lastname: Martinez
authors.forename: A
authors.initials: A
authors.lastname: Colmenarejo
authors.forename: M A
authors.initials: MA
authors.lastname: Saez
authors.forename: C
authors.initials: C
authors.lastname: Vallejo
authors.forename: J A
authors.initials: JA
authors.lastname: Martos
authors.forename: M
authors.initials: M
authors.lastname: Moreno
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012044:Regression Analysis