STAT3 as a biomarker of progression in atypical nevi of patients with melanoma: dose-response effects of systemic IFNalpha therapy.

Wang, Wenjun; Edington, Howard D; Rao, Uma N M; Jukic, Drazen M; Wang, Hong; Shipe-Spotloe, Janice M; Kirkwood, John M

Wang, Wenjun; Edington, Howard D; Rao, Uma N M; Jukic, Drazen M; Wang, Hong; Shipe-Spotloe, Janice M; Kirkwood, John M.

Afiliación

Wang W; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-2584, USA.

J Invest Dermatol ; 128(8): 1997-2002, 2008 Aug.

Article en En | MEDLINE | ID: mdl-18305569

RESUMEN

Signal transducer and activator of transcription (STAT3) plays a pivotal role in tumor progression. Atypical nevi are nonobligate risk markers of melanoma, affording investigators a target for evaluation of progression biomarkers in vivo. pSTAT1tyr701 (pSTAT1) and pSTAT3tyr705 (pSTAT3) oppose one another in biological function. Therefore, an analysis of phosphorylated STAT1 (pSTAT1) and pSTAT3 signaling was performed simultaneously using double-immunohistochemistry in biopsies of 168 atypical nevi from 42 patients receiving high- or low-dose IFNalpha (HDI and LDI). With maturation of melanocytes from junctional into dermal components of nevi, pSTAT1 expression increased, whereas pSTAT3 expression decreased. The percentage of pSTAT3-positive melanocytes was positively associated with the atypical degree of nevi (P<0.0001). In the junctional component of nevomelanocytic lesions, HDI and LDI downregulated the percentage of pSTAT3-positive melanocytes (P=0.008 and P=0.0003, respectively) while upregulating the percentage of pSTAT1-positive melanocytes (P=0.016 and P=0.0059, respectively) and augmented the pSTAT1/pSTAT3 ratio (P=0.008 and P=0.0040, respectively). It is suggested that the relative balance of pSTAT1/pSTAT3 may be associated with melanocyte differentiation in vivo. pSTAT3 is a potential biomarker of melanocytic transformation and progression and is modulated by IFNalpha dose-dependently. STAT3 is a potential target for chemoprevention of melanoma.

Asunto(s)

Biomarcadores de Tumor/metabolismo; Interferón-alfa/uso terapéutico; Melanoma/metabolismo; Nevo/metabolismo; Factor de Transcripción STAT3/metabolismo; Neoplasias Cutáneas/tratamiento farmacológico; Neoplasias Cutáneas/metabolismo; Biomarcadores de Tumor/genética; Biopsia; Progresión de la Enfermedad; Relación Dosis-Respuesta a Droga; Regulación Neoplásica de la Expresión Génica; Humanos; Factores Inmunológicos/uso terapéutico; Melanoma/tratamiento farmacológico; Melanoma/patología; Nevo/tratamiento farmacológico; Nevo/patología; Factor de Transcripción STAT1/genética; Factor de Transcripción STAT1/metabolismo; Factor de Transcripción STAT3/genética; Neoplasias Cutáneas/patología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Biomarcadores de Tumor / Interferón-alfa / Factor de Transcripción STAT3 / Melanoma / Nevo Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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