title: Absence of Granzyme B positive tumour-infiltrating lymphocytes in primary melanoma excisional biopsies is strongly associated with the presence of sentinel lymph node metastasis.
abstract: BACKGROUND
  Sentinel Lymph Node (SLN) status is strongly related to clinical outcome in melanoma patients. In this study we investigated the possible association between the presence of activated and/or suppressive Tumour Infiltrating Lymphocytes (TILs) and SLN status in clinically stage I/II melanoma patients.
  
  
  METHODS
  Diagnostic primary melanoma samples from 20 patients with a sentinel lymph node metastasis were compared to melanoma samples from 20 patients with a negative sentinel lymph node, who were matched for gender, age and Breslow thickness. Presence of activated Granzyme B positive (GrB+) TILs, presence of suppressive (FoxP3+) TILs and MHC class I antigen expression on tumour cells were analysed by immunohistochemistry.
  
  
  RESULTS
  FoxP3 and MHC-I expression had no direct bearing on the presence of melanoma metastases in the SLN. Whereas the presence of activated GrB+ TILs in the primary melanoma had no predictive value for SLN status either, their absence was strongly associated with the presence of metastasis in the SLN (p=0.001). While both GrB+ and FoxP3+ TILs could be detected in SLN metastases, a majority did not display MHC-I expression.
  
  
  CONCLUSIONS
  These data support a role for cytotoxic T cells in the prevention of early metastasis of melanoma to the draining lymph nodes.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: I S
authors.initials: IS
authors.lastname: van Houdt
authors.forename: B J R
authors.initials: BJ
authors.lastname: Sluijter
authors.forename: P A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: L M
authors.initials: LM
authors.lastname: Moesbergen
authors.forename: E
authors.initials: E
authors.lastname: Hooijberg
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: T D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: J J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: E
authors.initials: E
authors.lastname: Boven
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology*; D008875:Middle Aged
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D053804:Granzymes