Asunto(s)
Acné Vulgar/diagnóstico , Artritis Infecciosa/diagnóstico , Artritis Psoriásica/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Hidradenitis Supurativa/diagnóstico , Inmunosupresores/uso terapéutico , Fenotipo , Piodermia Gangrenosa/diagnóstico , Espondilitis Anquilosante/diagnóstico , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/genética , Acné Vulgar/inmunología , Adolescente , Adulto , Edad de Inicio , Anticuerpos Antifúngicos/sangre , Anticuerpos Antifúngicos/inmunología , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/genética , Artritis Infecciosa/inmunología , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/genética , Artritis Psoriásica/inmunología , Análisis Mutacional de ADN , Femenino , Heterogeneidad Genética , Pruebas Genéticas , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/inmunología , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/inmunología , Humanos , Masculino , Piodermia Gangrenosa/tratamiento farmacológico , Piodermia Gangrenosa/genética , Piodermia Gangrenosa/inmunología , Saccharomyces cerevisiae/inmunología , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/inmunología , Síndrome , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.
Asunto(s)
Antígenos Virales de Tumores/sangre , Biomarcadores de Tumor/sangre , Proteínas de la Cápside/sangre , Carcinoma de Células de Merkel/inmunología , Neoplasias Cutáneas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/mortalidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Poliomavirus de Células de Merkel/inmunología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/mortalidad , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/mortalidad , Pronóstico , Medición de Riesgo/métodos , Neoplasias Cutáneas/mortalidad , Infecciones Tumorales por Virus/inmunologíaRESUMEN
BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.