Melanoma gene expression and clinical course

Abstract

Evidence for the in vitro lymphocyte response against autologous melanoma has been accumulating over the past 10 years, leading to the identification of numerous melanoma-associated antigens recognised by T cells. These antigens are targets for specific immunotherapy protocols. However, their expression is heterogeneous during tumour progression and may contribute to therapeutic escape mechanisms and disease progression. This study was designed to chart the importance of these escape mechanisms, and to assess the relationship between gene expression and the clinical profile (especially survival data) of patients with melanoma. We studied the expression of certain melanoma genes in tissue biopsies from 202 patients using reverse transcriptase-polymerase chain reaction (RT-PCR). The evaluated genes were Melan-A, tyrosinase, Na-17A, MAGE-1, MAGE-3 and Ny-ESO-1. We then correlated the results to the patients' survival data. 202 samples (cutaneous, nodal and visceral biopsies) were analysed by RT-PCR. No relationship was found between clinical data and gene expression. No relationship was found between survival data and gene expression, when samples of all stages were combined in the analysis. However, interactions between gene expression and disease stage were significant. When stage III samples alone were considered, MAGE-3 expression alone or in association with the expression of the other tumour-specific genes was found to be significantly associated with a higher disease-free survival (respectively, P = 0.0349; 0.007). Our results provided no evidence for a relationship between gene expression and clinical data, or between gene expression and survival data. However, with regard to certain sub-groups, such as stage III samples, tumour gene expression was significantly associated with survival.

Germ Cell Proteins in Melanoma: Prognosis, Diagnosis, Treatment, and Theories on Expression

“…According to Vourc'H-Jourdain et al, MAGE-A3 was significantly related to an increase in disease-free survival when expressed in stage III melanoma patients [23]. …”

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

“…In general, tyrosinase expression is tightly controlled both spatially and temporally [21]. In tumor tissue, however, tyrosinase expression appears to be constitutively increased [21][22][23]. Furthermore, gray horses at increased risk of tumor formation (ADE Â 2) would be expected to have elevated tyrosinase expression in their melanocytes due to enhanced signaling from the MC1R pathway [18,21,24].…”

New York Esophageal Squamous Cell Carcinoma-1 and Cancer Immunotherapy

“…Desmoplastic melanoma 3/32 (9%)/IHC/E978 [56] Primary tumor 45%/IHC/E978 [35] Metastatic tumor 45%/IHC/E978 50/120 (42%)/qRT-PCR 48/120 (40%)/IHC/E978 [143] Stage I and stage II primary cutaneous melanoma 120/321(37%)/IHC/E978 [73] 12/38 (38%)/TMA (IHC) [114] Metastatic tumor 14/63 (23%)/RT-PCR [145] 10/23 (44%)/RT-PCR [146] 143/202 (71%)/RT-PCR [147] Melanoma Metastatic Humoral response in 12/127 (9.4%)/ELISA [94] Humoral response in 3/44 (7%)/ SEREX [148] 2/9 (2%)/RT-PCR Humoral response in 2/9 (2%)/ ELISA CD8 + T-cell responses/ ELISPOT [149] Humoral response in 17/148 (11%)/ELISA HLA-DP4 in 16/17 (94%) of seropositive patients CD4 + T cells specific for the NY-ESO-1 epitopes were generated from 5 of 6 melanoma patients with NY-ESO-1 Ab [150] Humoral response in 13/31 (42%)/ELISA CD4 + T cell 11/13 (85%) of seropositive patients/ ELISPOT [151] 22/39 (56%)/IHC/E978 [152] Primary tumor 8/61 (13%)/IHC/E978 [54] Metastatic Metastatic 53/55 (96%)/IHC/D8.38 [154] Squamous cell carcinoma 32/109 (29%)/TMA [155] 6/9 (67%)of mRNA positive samples/IHC/ ES121 [114] Humoral response in 4/20 (20%)/SEREX and ELISA [161] 9/23 (39%)/RT-PCR Humoral response in 12/23 (52%) patients and in 5/9 (55%) of NY-ESO-1 expressing tumors/ ELISA [162] 78/92 (85%)/IHC/D8.38 [127] 3/20 (15%)/IHC/D8.38…”