RESUMEN
BACKGROUND: Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS mutations. OBJECTIVES: We sought to determine whether NS-related and NS-unrelated trichilemmomas harbour RAS mutations. METHODS: Formalin-fixed and paraffin-embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also analysed for NS-unrelated cases. RESULTS: Among the 27 cases, mutually exclusive HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations, including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested. CONCLUSIONS: The high frequency of HRAS activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.
Asunto(s)
Genes ras/genética , Mutación/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Cutáneas/genética , Fosfatidilinositol 3-Quinasa Clase I , Exones/genética , Genotipo , Enfermedades del Cabello/genética , Folículo Piloso , Humanos , Tasa de Mutación , Neoplasias Basocelulares/genética , Fosfatidilinositol 3-Quinasas/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
BACKGROUND: Angiogenic factors have an essential role in normal and pathologic angiogenesis. However, the clinical implication of angiogenic factor expression in myelodysplastic syndromes (MDS) remains unclear. METHODS: In this study, we sought to investigate the prognostic impact of the expression of genes encoding angiopoietin-1 (Ang-1), Ang-2, the receptor Tie2, vascular endothelial growth factor-A (VEGF-A) and VEGF-C in the bone marrow (BM) in 208 patients with newly diagnosed primary MDS. RESULTS: BM Ang-1 expression was significantly higher in MDS patients, especially those with higher-risk subtypes, than in normal controls. With a median follow-up time of 32.9 months, the disease transformed to acute leukaemia more frequently in the patients bearing higher Ang-1 expression than in those with lower expression (31.5% vs 18.6%, P=0.023). The MDS patients with higher Ang-1 expression had shorter overall survival than those with lower expression (median 20.8±4.5 months vs 63.3±17.8 months, P<0.001). Multivariate analyses showed that higher Ang-1 expression was an independent unfavourable prognostic factor for overall survival. There was no impact of the expression of other angiogenic factors on survival. CONCLUSION: BM Ang-1 expression may serve as a new biomarker to predict clinical outcome in MDS patients.