RESUMEN
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.
Asunto(s)
Antígenos de Neoplasias/genética , Predisposición Genética a la Enfermedad , Melanoma/genética , Proteínas de Transporte de Membrana/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Haplotipos , Humanos , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Mutación , Riesgo , EspañaRESUMEN
BACKGROUND: Granular cell tumor (GCT), also known as Abrikossoff tumor, is an uncommon benign neoplasm, probably of neural origin derived from Schwann cells. It presents clinically as a solitary asymptomatic nodule and its pathogenesis has been the subject of much debate in the literature. OBJECTIVES: We aimed to analyze the clinical, histologic, and immunohistochemical characteristics associated with this tumor and to determine whether these findings correspond to those reported to date in the literature. METHODS: In this retrospective study of 34 patients with histologic diagnosis of GCT, we analyzed clinical characteristics (site, age, sex, duration, and suspected diagnosis), histological findings (border, cell atypia and mitoses, involvement of adnexal structures, pseudoepitheliomatous hyperplasia, and presence of the recently described pustulo-ovoid bodies), and immunohistochemical findings (S-100 staining in 16 randomly selected cases). RESULTS: In total, 58.82 % were men and 41.18 % were women, and the mean age was 31.74 years. The most common site was the oral cavity (61.76 %). The most frequently suspected clinical diagnosis was fibroma (17.65 %). The lesion was poorly defined and diffuse in 85.29 %. Pseudoepitheliomatous hyperplasia was present in 58.82 %. Nuclear atypia was found in 29.41 % and mitoses in 20.59 %. One case was considered malignant (2.94 %) and 2 atypical (5.88 %). Pustulo-ovoid bodies were present in 47.06 % of the cases and S-100 staining was positive in all cases analyzed. CONCLUSIONS: Our series confirms the characteristics described previously for GCT, except for certain peculiarities, and supports the presence of pustulo-ovoid bodies as an additional histologic finding for diagnosis of this tumor.