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Tyrosinase expression in the peripheral blood of stage III melanoma patients is associated with a poor prognosis: a clinical follow-up study of 110 patients.

ABSTRACT: The aim of this study is to define the relationship between the tyrosinase expression in the peripheral blood and the clinical course of the disease in stage III disease-free melanoma patients after radical lymph node dissection. RT-PCR techniques were used to identify tyrosinase mRNA in 110 patients; a total of 542 blood samples were investigated. In all, 54 patients (49%) showed at least one positive result; 13 patients (11.8%) showed baseline positive results: six became negative thereafter, whereas seven showed follow-up positive results until disease progression occurred. One or more positive determinations were found during follow-up in 41 patients with negative baseline tyrosinase. No correlation was found between baseline results and the relapse rate or disease-free survival (DFS), whereas a significant correlation was found between positive tyrosinase results and disease recurrence during follow-up. In fact, 72.9% of positive patients relapsed, but only 19.3% of negative cases did so. The median interval between the positive results and the clinical demonstration of the relapse was 1.9 months (range 1-6.6). Disease-free survival multivariate analysis selected, as independent variables, Breslow thickness (P=0.05), lymph node involvement according to the AJCC classification (P=0.05) and tyrosinase expression (P=0.0001). In conclusion, RT-PCR tyrosinase mRNA expression is a reliable and reproducible marker associated with a high risk of melanoma progression and we encourage its clinical use in routine follow-up.

SUBMITTER: Osella-Abate S

PROVIDER: S-EPMC2394348 | biostudies-other | 2003 Oct

REPOSITORIES: biostudies-other

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Project description:BackgroundWith more than 15,000 new cases /year in France and 2,000 deaths, cutaneous melanoma represents approximately 4% of incidental cancers and 1.2% of cancer related deaths. In locally advanced (stage III) or resectable metastatic (stage IV) melanomas, medical adjuvant treatment is proposed and recent advances had shown the benefit of anti-PD1/PDL1 and anti-CTLA4 immunotherapy as well as anti-BRAF and anti-MEK targeted therapy in BRAF V600 mutated tumors. However, the recurence rate at one year is approximately 30% and justify extensive research of predictive biomarkers. If in metastatic disease, the follow-up of circulating tumor DNA (ctDNA) has been demonstrated, its interest in adjuvant setting remains to be precised, especially because of a lower detection rate. Further, the definition of a molecular response could prove useful to personalized treatment.MethodsPERCIMEL is an open prospective multicentric study executed through collaboration of the Institut de Cancérologie de Lorraine (non-profit comprehensive cancer center) and 6 French university and community hospitals. A total of 165 patients with resected stage III and IV melanoma, eligible to adjuvant imunotherapy or anti-BRAF/MEK kinase inhibitors will be included. The primary endpoint is the presence of ctDNA, 2 to 3 weeks after surgery, defined as mutated ctDNA copy number calculated as the allelic fraction of a clonal mutation relative to total ctDNA. Secondary endpoints are recurrence-free survival, distant metastasis-free survival and specific survival. We will follow ctDNA along treatment, quantitatively through ctDNA mutated copy number variation, qualitatively through the presence of cfDNA and its clonal evolution. Relative and absolute variations of ctDNA during follow-up will be also analyzed. PERCIMEL study aims at provide scientific evidence that ctDNA quantitative and qualitative variations can be used to predict the recurrence of patients with melanoma treated with adjuvant immunotherapy or kinase inhibitors, thus defining the notion of molecular recurrence.

Project description:Fatty acid-binding protein 5 (FABP5), which participates in mediating the biological properties of tumor cells, has been recognized in several neoplasms. The present study aims to investigate FABP5 transcriptional expression profiles, reveal its underlying biological interaction networks and define its prognostic value in uveal melanoma (UVM). A total of 80 patients with UVM and their RNA-sequence data, available from The Cancer Genome Atlas (TCGA) database, was analyzed. A differential transcriptional expression profile was obtained from TCGA and the Oncomine databases. The survival benefits were analyzed using the Kaplan-Meier method and log-rank test. The correlation between FABP5 expression and immune infiltration level was analyzed using the Tumor Immune Estimation Resource database. Functional enrichment analyses using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and signaling hallmarks were utilized to describe the biological process, molecular functions, cellular component and significantly involved pathways. The elevated transcriptional expression of FABP5 was significantly associated with shorter overall survival (OS) and worse progression-free survival (PFS) times in patients with UVM (P<0.001). Moreover, FABP5 expression was significantly and positively correlated with tumor purity and CD8+ T cells and was negatively correlated with the infiltrating levels of CD4+ T cells and neutrophils. Gene Set Enrichment Analysis was performed to obtain 100 significantly associated genes of FABP5 and FABP5 was found to be critical in several hallmark pathways, including allograft rejection, complement, interleukin-6/Janus kinase-STAT3 signaling, interferon γ response, inflammatory response and tumor necrosis factor α signaling via NFκB. The present study is the first to demonstrate that FABP5 expression was positively associated with progression-associated clinicopathological factors and poor prognosis in UVM, which suggests its likely function as an oncogene and prognostic marker in patients with UVM.

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Tyrosinase expression in the peripheral blood of stage III melanoma patients is associated with a poor prognosis: a clinical follow-up study of 110 patients.

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