Absence of Granzyme B positive tumour-infiltrating lymphocytes in primary melanoma excisional biopsies is strongly associated with the presence of sentinel lymph node metastasis
Affiliations: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands | Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands | Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Note: [] Both authors contributed equally to this work.
Note: [] Corresponding author: Erik Hooijberg, PhD, Cancer Center Amsterdam, Department of Pathology (CCA 2-26), VU University Medical Center, de Boelelaan 1117, NL 1081 HV, P.O. Box 7057, NL-1007 MB, Amsterdam, The Netherlands. Tel.: +31 20 4444041; Fax: +31 20 4442964; E-mail: erik.hooijberg@vumc.nl.
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. Conclusion: These data support a role for cytotoxic T cells in the prevention of early metastasis of melanoma to the draining lymph nodes.
