RESUMO
We report the case of a newborn boy with multinodular NRAS and BRAF mutation-negative congenital melanocytic nevi and cerebral lesions compatible with congenital intraparenchymal melanosis. Histopathology from skin lesions showed atypical nodular melanocytic proliferation with marked melanocytic atypia and a large number of mitoses and apoptosis, indicating aggressive proliferation. The child developed several new subcutaneous tumors and multiple internal lesions, which were confirmed to be metastases, and died at 5 months of age. This case may represent an infantile melanoma developing from a giant congenital melanocytic nevus or a congenital melanoma.
Assuntos
GTP Fosfo-Hidrolases/genética , Melanoma/patologia , Proteínas de Membrana/genética , Nevo Pigmentado/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia , Evolução Fatal , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Melanose/patologia , Mutação , Nevo Pigmentado/genética , Pele/patologia , Neoplasias Cutâneas/genética , UltrassonografiaRESUMO
The transmembrane transporter P-glycoprotein (P-gp) encoded by ABCB1, is one major cause for multidrug resistance (MDR). We compared the genomic profile and gene expression pattern of the P-gp positive K562VCR cells with parental P-gp negative K562wt cells. In K562VCR array CGH revealed amplification of ABCB1, ABCB4, ABCB5 and SEMA3D, whereas expression microarrays demonstrated upregulation of stem cell genes (e.g. KIT and HOXB4), anti-apoptotic genes (e.g. IGF1R and CCNG1), and downregulation of pro-apoptotic genes (e.g. CASP4, 6 and 7). Thus, K562VCR cells disclose stem cell characteristics including a range of drug resistance mechanisms possibly attained as a stem cell program switched on en bloc.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Células K562/patologia , Leucemia Eritroblástica Aguda/genética , Mapeamento Cromossômico , Cromossomos Humanos , Citometria de Fluxo , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Fator de Células-Tronco/genética , Células-Tronco/citologia , Células-Tronco/fisiologia , Fatores de Transcrição/genética , Regulação para CimaRESUMO
BACKGROUND: Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence and prognostic value of activated phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2) and cyclo-oxygenase-2 (COX-2) both at the invasive front and in central/superficial parts of OSCCs. METHODS: Using immunohistochemistry, we assessed the presence of p-ERK1/2 and COX-2 in 53 early stage OSCCs. Clinical data were recorded prospectively. The end point was disease-free survival. RESULTS: p-ERK1/2 staining was present in almost all tumours. The staining was mostly nuclear in the cells of the invasive front and either nuclear or nuclear/cytoplasmic in central/superficial tumour parts. COX-2 was observed in almost all tumours (98%) and the staining was often restricted to focal areas. Most tumours were COX-2 negative at the invasive front. The lowest P-value in survival analyses was P = 0.06 for p-ERK1/2 at the invasive front. COX-2, the histomorphological grading systems and TNM stage were of no prognostic value. CONCLUSION: p-ERK1/2 was present in almost all tumours and p-ERK1/2 may be a prognostic marker at the invasive front of OSCCs. In early stage OSCCs, most tumours did not express COX-2 at the invasive front.
