title: Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma.
abstract: Various clinical and experimental observations detected an immunological host defense in cutaneous melanoma. In order to investigate the prognostic value of leukocyte effector mechanisms, we examined the presence of different subsets of leukocytes in tumor samples of 58 patients diagnosed with primary cutaneous melanoma. The presence of T lymphocytes, cytotoxic T lymphocytes, B lymphocytes, CD16+ cells and macrophages was correlated to Breslow depth. A significantly higher amount of several subsets of leukocytes was found in samples with a more progressed tumor stage and survival analysis demonstrated that a higher amount of T lymphocytes and CD16+ cells was associated with a short survival. The amount of FOXP3+ regulatory T lymphocytes did not correlate with survival, nevertheless, it correlated with the amount of total infiltrate. In contrast, analysis of the expression of CD69, a marker for activated lymphocytes, demonstrated that patients with a higher amount of CD69+ lymphocytes had a better survival. In addition, a new parameter for aggressiveness of melanoma, tumor cell plasticity [i.e., the presence of periodic acid Schiff's (PAS) reagent positive loops], also predicted short survival and a trend of a higher amount of tumor infiltrating leukocytes in tumors with PAS positive loops was observed. These findings demonstrate that leukocyte infiltration and the presence of PAS loops is a sign of tumor aggressiveness and may have prognostic value.
authors.affiliation: Angiogenesis Laboratory, Department of Pathology, Research Institute for Growth and Development (GROW), University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Hillen
authors.forename: Coen I M
authors.initials: CI
authors.lastname: Baeten
authors.forename: Anouk
authors.initials: A
authors.lastname: van de Winkel
authors.forename: David
authors.initials: D
authors.lastname: Creytens
authors.forename: Daisy W J
authors.initials: DW
authors.lastname: van der Schaft
authors.forename: Véronique
authors.initials: V
authors.lastname: Winnepenninckx
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012878:Skin Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D016019:Survival Analysis; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D000099192:CD69 Antigens