RESUMEN
BACKGROUND: Mutations of BRAF, NRAS and c-KIT oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features. BRAF-, MEK- and KIT-inhibitors led to improvement in overall survival of patients harbouring mutated metastatic melanoma. OBJECTIVES: To assess the prevalence and types of BRAF, NRAS, c-KIT and MITF mutations in cutaneous and mucous melanoma and to correlate mutation status with clinicopathological features and outcome. METHODS: Clinicopathological features and mutation status of 108 samples and of 98 consecutive patients were, respectively, assessed in one retrospective and one prospective study. Clinicopathological features were correlated with mutation status and the predictive value of these mutations was studied. RESULTS: This work identified significant correlations between BRAF mutations and melanoma occurring on non-chronic sun-damaged skin and superficial spreading melanoma (P < 0.05) on one hand, and between NRAS mutations and nodular melanoma (P < 0.05) on the other hand. Younger age (P < 0.05), microscopic (P < 0.05) and macroscopic (P < 0.05) lymphatic involvement at diagnosis of primary melanoma were significantly linked to BRAF mutations. A mutated status was a positive predictive factor of a response to BRAF inhibitors (OR = 3.44). Mutated melanoma showed a significantly (P = 0.038) higher objective response rate to cytotoxic chemotherapy (26.3%) than wild-type tumours (6.7%). CONCLUSION: Clinical and pathological characteristics of the primary melanoma differed between wild-type and BRAF- or NRAS-mutated tumours. Patients with BRAF-mutated tumours were younger at diagnosis of primary melanoma. Patients carrying mutations showed better responses better to specific kinase inhibitors and interestingly also to systemic cytotoxic chemotherapy.
Asunto(s)
GTP Fosfohidrolasas/genética , Melanoma/genética , Proteínas de la Membrana/genética , Factor de Transcripción Asociado a Microftalmía/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Neoplasias Cutáneas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
Assessment of anti-tumor treatment efficiency is usually done by measuring tumor size. Treatment may however induce changes in the tumor other than tumor size. Magnetic Resonance Imaging Texture Analysis (MRI-TA) is presently used to follow activated lymphocyte cell therapy. We used a 7T microimager to acquire high-resolution MR images of an experimental liver metastasis from colon carcinoma in rats treated (n = 4) or not (n = 3) with a cell therapy product. MRI-TA was then performed with Linear Discriminant Analysis and showed: i) a significant variation of tumor texture with tumor growth and ii) a significant modification in the texture of tumors treated with activated lymphocytes compared with untreated tumors. T2-weighted images or volume calculation did not evidence any difference. MRI-TA appears as a promising method for early detection and follow-up of response to cell therapy.
Asunto(s)
Adenocarcinoma/secundario , Adenocarcinoma/terapia , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Inmunoterapia Adoptiva/métodos , Neoplasias Hepáticas Experimentales/secundario , Neoplasias Hepáticas Experimentales/terapia , Imagen por Resonancia Magnética/métodos , Adenocarcinoma/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Neoplasias del Colon/inmunología , Neoplasias Hepáticas Experimentales/inmunología , Activación de Linfocitos/inmunología , Masculino , Monitorización Inmunológica/métodos , Monitoreo Fisiológico/métodos , RatasRESUMEN
The authors report a case of renal metastasis from a follicular carcinoma of the thyroid in a 62-year-old man, occurring 7 years after isthmolobectomy for thyroid carcinoma. Clinical symptoms radiographics results and treatment are discuss after a review of the literature.
