Differential expression of E-cadherin gene in human neuroepithelial tumors

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of ú0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

Lack of evidence for mutations or deletions in the CDKN2A/p16 and CDKN2B/p15 genes of Brazilian neuroblastoma patients

Neuroblastoma, the most common extracranial tumor in childhood, has a wide spectrum of clinical and biological features. The loss of heterozygosity within the 9p21 region has been reported as a prognostic factor. Two tumor suppressor genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell cycle progression and are considered to be targets for tumor inactivation. We analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent stage of the tumor was stage IV (50 percent), followed by stages II and III (20 percent) and stage I (10 percent). The samples were submitted to the multiplex PCR technique for homozygous deletion analysis and to single-strand conformation polymorphism and nucleotide sequencing for mutation analysis. All exons of both genes were analyzed, but no deletion was detected. One sample exhibited shift mobility specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing. Homozygous deletions and mutations are not involved in the inactivation mechanism of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two abnormalities do not exclude other inactivation pathways. Recent evidence has shown that the expression of these genes is altered in this disease. Therefore, other mechanisms of inactivation, such as methylation of promoter region and unproperly function of proteins, may be considered in order to estimate the real contribution of these genes to neuroblastoma genesis or disease progression.

Poliploidia em Tumor de Wilms / Polyploidia in tumor of Wilms

Os autores analisam citogeneticamente celulas derivadas de um tumor de Wilms objetivando estabelecer correlacao entre poliploidia e histologia desfavoravel. O exame citogenetico do caso foi realizado por metodo diretocom analise de 20 metafases, que revelou poliploidia em 100% das celulas analisadas, com variacao de 60 a 69 cromossomos. O resultado histologico foi do tipo blastemal anaplasico. Os dados sao consistentes com outros da literatura realizados tanto com exame citogenetico como atraves de analise de DNA por citometria de fluxo, que associam poliploidia com histologia desfavoravel e confirmam o exame citogenetico como um elemento importante na avaliacao do prognostico desta neoplasia .

Valores sericos de zinco em criancas com hemoglobinopatia (anemia falciforme, beta talassemia e S-talassemia). / Serum zinc levels in children with hemoglobinopathy (sickle cell anemia, beta-thalassenia and S-thalassemia)

Foram observados, na regiao de Ribeirao Preto, os valores sericos de zinco, cobre e ferro em 24 criancas com hemoglobinopatia (nove com anemia falciforme, 10 com beta-talassemia e cinco com S-talassemia) com idade compreendida entre seis e 144 meses. Os resultados mostraram que existe diminuicao da concentracao do zinco nestes pacientes, sendo mais evidente nas criancas com beta-talassemia. Ocorre aumento da concentracao do cobre serico.Ha aumento da concentracao do ferro serico apenas nas criancas com beta-talassemia. Nao foi encontrada correlacao entre os niveis de zinco e os de cobre e ferro, bem como entre os niveis de zinco e o deficit pondero-estatural

Zinco na desnutricao proteico-calorica.I. Concentracao no soro de criancas com os tipos clinicos kwashiorkor e kwashiorkor-marasmatico. / Zinc in protein-calorie malnutrition. I. Concentration in serum of children with clinical features of kwashiorkor and marasmatic kwashiorkor

Foram determinadas as concentracoes sericas de zinco em 10 criancas com desnutricao proteico-calorica (oito com tipo clinico kwashiorkor e duas com o tipo kwashiorkor-marasmatico), no primeiro, decimo quinto e trigesimo dias de internaco. Nestes pacientes os niveis de zinco, no primeiro dia foram significativamente inferiores aqueles observados em criancas com bom estado nutricional. Durante o periodo inicial de recuperacao do estado nutricional, nao houve aumento significativo da concentracao deste oligoelemento no soro. E discutida a possibilidade de suplementacao deste cation durante a recuperacao de criancas desnutridas