neuropeptide-y and Melanoma

Neuropeptide Y (NPY) is involved in the carcinogenesis of different tumours, especially neural crest-derived tumours.. The aim of our study is to investigate the expression of NPY on melanoma and its relation with prognostic histological parameters and survival.. This is a retrospective observational study of two independent series, with a total of 79 primary melanomas, diagnosed in two independent University Hospitals in Spain, from January 2000 to December 2004.. We found a significant higher expression of NPY on superficial spreading melanoma and lentigo maligna (40%) (P = 0.030). Thinner tumours were associated with higher NPY expression (Clark level, P = 0.003; Breslow level, P = 0.012). Melanomas with low NPY expression were associated with intense cell proliferation (Ki-67, P = 0.034), high density of peritumoral mast cell infiltrates (P = 0.033) and low E-cadherin expression (P = 0.031). Melanomas with high NPY expression exhibited significant differences in terms of relapse time (median: 114 vs. 68 months, P = 0.008) and overall survival (114 vs. 74 months, P = 0.004).. High expression of NPY was associated with better prognostic histological parameters, low peritumoral mast cells density, presence of adhesion proteins and better outcome.

Topics: Adult; Aged; Aged, 80 and over; Cadherins; Cell Proliferation; Disease-Free Survival; Female; Humans; Hutchinson's Melanotic Freckle; Ki-67 Antigen; Male; Mast Cells; Melanoma; Middle Aged; Neuropeptide Y; Retrospective Studies; Skin Neoplasms; Survival Rate; Tumor Burden

Neuropeptide Y (NPY) is widely found in the nervous system and has a role in numerous physiologic processes. In addition, NPY receptors are expressed in neuroendocrine tumors, breast cancer, prostate cancer, kidney cancer, and some types of sarcomas. Different neuropeptides, particularly α-melanocyte-stimulating hormone (MSH), seem to play a role in the pathogenesis of melanoma.. We sought to analyze the expression of NPY in cutaneous melanoma, its association with clinical and histologic features, and its correlation with α-MSH.. This was an observational study of the immunohistochemical expression of NPY and α-MSH in tissue samples of cutaneous melanomas, different types of melanocytic nevi, and melanoma metastases diagnosed from 2004 to 2008 in San Jorge Hospital, Huesca, Spain.. A total of 184 lesions were studied: 49 primary cutaneous melanomas, 12 melanoma metastases (9 cutaneous and 3 lymphatic), and 123 melanocytic nevi. Immunostaining revealed that levels of NPY and α-MSH were significantly higher in melanomas than in melanocytic nevi (P < .001). Melanoma metastases were negative for both neuropeptides. Nodular melanomas showed the highest median percentage of NPY positive cells (75% [20-95]) followed by superficial spreading melanoma (25% [2-92]), whereas lentigo maligna were negative (0% [0-0]). Significant, direct associations between NPY expression and vertical growth (P = .0141) and presence of metastasis (P = .0196) were observed. NPY and α-MSH were positively correlated in cutaneous melanoma (0.49, P < .001).. The sample size of melanomas was not very large.. Our study demonstrates that NPY is significantly expressed in melanomas, especially the nodular type, being associated with invasiveness independently of proliferative markers such as thickness, ulceration, and mitotic index.

Topics: Aged; alpha-MSH; Female; Hormones; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Melanoma; Middle Aged; Mitotic Index; Neoplasm Invasiveness; Neuropeptide Y; Nevus, Pigmented; Skin Neoplasms

Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in remission since 1994 following adjuvant TIL immunotherapy, with the autologous melanoma cell line. They were cloned by limiting dilution. One CTL clone recognized melanoma cell lines expressing tyrosinase and the B*4002 molecule, either spontaneously or upon transfection. We demonstrated that this clone recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the overlapping decapeptide 315-324 (SADVEFCLSL). We derived two distinct additional specific CTL clones from this same patient that were also reactive against B*4002 melanoma cell lines, suggesting a relative diversity of this specific repertoire in this patient. Stimulating PBMC derived from four additional B*4002 melanoma patients with the tyrosinase 316-324 nonapeptide induced the growth of specific cells for two of the patients, demonstrating the immunogenicity of this new epitope. Our data show that this nonapeptide is a new tool that could be used to generate melanoma-specific T cells for adoptive immunotherapy or serve as a peptide vaccine for HLA-B*4002 melanoma patients.

Topics: Amino Acid Sequence; Animals; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; DNA, Complementary; Epitopes; Galanin; HLA-B Antigens; Humans; Leukocytes, Mononuclear; Melanoma; Mice; Molecular Sequence Data; Monophenol Monooxygenase; Neuropeptide Y; Peptide Fragments; Peptides; T-Lymphocytes, Cytotoxic