[en] Background:Clinical outcome of patients with high-risk melanoma cannot be reliably predicted on the basis of classical histopathological examination. Our study aimed to determine in melanoma metastases a gene expression profile associated with patient survival, and to identify and validate marker(s) of poor clinical outcome.Methods:Skin and lymph node metastases from melanoma patients (training population) were used to identify candidate prognostic marker(s) based on DNA microarray analysis. Additional skin metastases (validation population) were used to assess the prognostic value of the first ranked gene by real-time PCR.Results:We performed microarray analysis in the training population and generated a list of 278 probe sets associated with a shorter survival. We used the first ranked gene, tyrosinase-related protein 1 (TYRP1), further measured its expression in the validation population by real-time PCR and found it to be significantly correlated with distant metastasis-free survival (DMFS), overall survival (OS) and Breslow thickness. We also found that it was fairly well conserved in the course of the disease regardless of the delay to metastasis occurrence. Finally, although Tyrp1 protein (immunohistochemistry (IHC)) was only detected in about half of the samples, we showed that its expression also correlated with Breslow thickness.Conclusion:Our data indicate that TYRP1 mRNA expression level, at least in skin metastases, is a prognostic marker for melanoma, and is particularly useful when prognostic pathology parameters at the primary lesion are lacking. Its conserved expression further supports its use as a target for therapy.
Disciplines :
Immunology & infectious disease Oncology
Author, co-author :
Journé, Fabrice
Id Boufker, Hichame
Van Kempen, Léon
Galibert, Marie-Dominique
Wiedig, Murielle
Salès, François
Theunis, Anne
Nonclercq, Denis ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Histologie
Frau, Annica ; Université de Mons > Faculté de Médecine et de Pharmacie > Histologie ; Université de Mons > Faculté de Médecine et de Pharmacie > Biologie humaine et Toxicologie
Laurent, Guy ; Université de Mons > Faculté de Médecine et de Pharmacie > Histologie
Awada, Ahmad
Ghanem, Ghanem
Language :
English
Title :
TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome
Publication date :
22 November 2011
Journal title :
British Journal of Cancer
ISSN :
0007-0920
Publisher :
Nature Publishing Group, United Kingdom
Volume :
105
Issue :
11
Pages :
1726-1732
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M118 - Histologie
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
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