RESUMO
BACKGROUND: Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s ('s': standard form) cell adhesion molecule by comparison with other specific prognostic markers. METHODS: An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. RESULTS: Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. DISCUSSION: These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863
Assuntos
Biomarcadores Tumorais/análise , Ganglioneuroma/imunologia , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Neuroblastoma/imunologia , Adolescente , Biomarcadores Tumorais/genética , Diferenciação Celular , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Fixadores , Formaldeído , Ganglioneuroblastoma/genética , Ganglioneuroblastoma/imunologia , Ganglioneuroblastoma/patologia , Ganglioneuroma/genética , Ganglioneuroma/patologia , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Funções Verossimilhança , Modelos Lineares , Modelos Logísticos , Masculino , Marrocos , Análise Multivariada , Proteína Proto-Oncogênica N-Myc , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/patologia , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Inclusão em Parafina , Prognóstico , Estudos Retrospectivos , Fixação de Tecidos/métodos , Regulação para CimaRESUMO
BACKGROUND: Cryptorchidism is the most common genital anomaly in men. The INSL3/LGR8 system is involved in testicular descent via gubernacular development. INSL3 binds with high affinity to its receptor LGR8 and receptor activation is associated with cAMP signaling. Analysis of human INSL3 and LGR8 mutations confirms that some cases of cryptorchidism are caused by mutations in these genes. The T222P mutation is the only one within the LGR8 gene associated with the cryptorchidism phenotype. A strong association of the T222P mutation with cryptorchidism was found in an Italian population. Due to the same mutation being found in patients within the Mediterranean area, a possible founder effect of this mutation is supposed. METHODS: We screened 109 patients with cryptorchidism and 250 controls in a Moroccan population. RESULTS: We found that 3 of the 109 patients tested carry the T222P mutation and 4 individuals in the control group also carry the mutation. CONCLUSIONS: Our results show in fact that the same mutation is present in the Moroccan population, but an association between cryptorchidism and the T222P mutation was not found.
Assuntos
Substituição de Aminoácidos , Criptorquidismo/genética , Mutação de Sentido Incorreto , Receptores Acoplados a Proteínas G/genética , Criptorquidismo/metabolismo , Criptorquidismo/fisiopatologia , AMP Cíclico/genética , AMP Cíclico/metabolismo , Efeito Fundador , Humanos , Insulina/genética , Insulina/metabolismo , Masculino , Marrocos , Proteínas/genética , Proteínas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genéticaRESUMO
PURPOSE: Cryptorchidism affects 1% to 9% of full-term male neonates. Hypospadias is the second most frequent congenital anomaly seen in newborn males. These pathological conditions are part of the testicular dysgenesis syndrome. Insulin-like factor 3 and LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8), acting as a hormone and a receptor, respectively, are involved in control of the first phase of testicular descent via gubernacular development. MATERIALS AND METHODS: The study group consisted of 184 patients, of whom 52 presented with unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19 presented with cryptorchidism and hypospadias, 1 presented with bilateral cryptorchidism and micropenis, and 75 presented with isolated hypospadias. A control panel consisted of 270 controls, including 127 fertile, and 143 fertile noncryptorchid males. Insulin-like factor 3 mutations were analyzed by direct sequencing and restriction enzyme digestion. We analyzed the ability of the mutant insulin-like factor 3 peptides identified in this study to activate LGR8 receptor in an ex vivo assays. RESULTS: We identified 3 novel insulin-like factor 3 variants, including C-19G, V18M and R105H, in 3 of the 109 patients (2.75%) but in none of the 270 controls. The V18M mutation in the insulin-like factor 3 signal peptide had a significant deleterious effect in activating LGR8 receptor in ex vivo studies (p<0.05). To our knowledge we report the first variant in the promoter region of the insulin-like factor 3 gene in a patient with cryptorchidism in association with micropenis. CONCLUSIONS: Mutations involving the insulin-like factor 3 gene may contribute to other anomalies of male genital development, such as micropenis.