Absence of Granzyme B positive tumour-infiltrating lymphocytes in primary melanoma excisional biopsies is strongly associated with the presence of sentinel lymph node metastasis.
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.
van Houdt
I S
IS
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Sluijter
B J R
BJ
van Leeuwen
P A M
PA
Moesbergen
L M
LM
Hooijberg
E
E
Meijer
C J L M
CJ
de Gruijl
T D
TD
Oudejans
J J
JJ
Boven
E
E
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
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D053804:Granzymes