title: CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.
abstract: OBJECTIVE
  Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery.
  
  
  METHODS
  Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.
  
  
  RESULTS
  CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting.
  
  
  CONCLUSIONS
  T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.
authors.forename: Viktor H
authors.initials: VH
authors.lastname: Koelzer
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Heather
authors.initials: H
authors.lastname: Dawson
authors.forename: Marion
authors.initials: M
authors.lastname: Hädrich
authors.forename: Martin D
authors.initials: MD
authors.lastname: Berger
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
authors.forename: Makhmudbek
authors.initials: M
authors.lastname: Mallaev
authors.forename: José A
authors.initials: JA
authors.lastname: Galván
authors.forename: Jennifer
authors.initials: J
authors.lastname: Amsler
authors.forename: Beat
authors.initials: B
authors.lastname: Schnüriger
authors.affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr, 31, Bern CH-3010, Switzerland. inti.zlobec@pathology.unibe.ch.
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Daniel
authors.initials: D
authors.lastname: Inderbitzin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods*; D016827:CD8 Antigens / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; D017493:Leukocyte Common Antigens