RESUMO
BACKGROUND & OBJECTIVE: p53 gene plays an important role in regulating cell cycle, maintaining completeness of cellular genomes, inducing cell differentiation and apoptosis. p53 gene mutation occurs usually in gliomas, especially astrocytomas. This study was to investigate p53 gene mutation and its correlation to the development of glioma. METHODS: p53 gene mutation in 41 specimens of human gliomas was analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing. RESULTS: p53 gene mutations were found in 17 (41.5%) of the 41 specimens of gliomas. The p53 mutations located on exons 5-8: 7 cases (41.2%) on exon 5; 1 (5.9%) on exon 6; 4 (23.5%) on exon 7; 5 (29.4%) on exon 8. The mutation rate of p53 gene was significantly higher in grade III-IV gliomas than in grade I-II gliomas (P<0.01). DNA sequencing indicated that the p53 gene mutations were point mutations and deletions of exons in the 17 positive cases, including 13 cases (76.5%) of missense mutation, 2 cases (11.8%) of samesense mutation, and 2 cases (11.8%) of frame shift mutation. G_A and A-->G were major base mutations (55.6%). CONCLUSIONS: p53 mutations always locate on exons 5 and 8. Missense mutation is major mutant type of p53 gene. p53 mutation plays an important role in the development and malignant transformation of human gliomas.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Genes p53/genética , Mutação de Sentido Incorreto , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Sequência de Bases , Criança , Éxons , Feminino , Mutação da Fase de Leitura , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Adulto JovemRESUMO
To investigate the effect of P53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, P53 and P16 protein in glioma formation and progression and their relationship with each other, LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of MDM2, P53 and P16 protein and p53 gene mutation in 48 cases of gliomas. The results showed that the positive expression rate of MDM2, P53 and the negative rate of P16 was 22.9%, 41.7% and 60.4%, respectively. The latter two in high grade (grade III, IV) gliomas had a significantly higher rate than in the low grade (grade II) gliomas. Moreover, the co-expression of MDM2 and P53 protein was confirmed in only 1 of 48 cases. No significant difference was found in the rate of the expression of MDM2 between high grade and low grade gliomas (P > 0.1). PCR-SSCP results showed that mutation of 5-8 exons of p53 gene was detected in 17 out of 48 cases (35.42%). Mutation was detected in 16 of 20 cases of positive p53 expression, and another one was detected in 28 cases of negative expression cases. The correlation between p53 mutation and p53 immunopositivity was observed in 89.6% of the cases. P53 gene mutation and the level of MDM2, P53 and P16 protein were not related to age, gender of the patients, tumor location and size. It is concluded that the mutation of p53 and deletion of p16 might play important roles in the tumorigenesis of gliomas and it was significantly associated with the grade of tumor differentiation. P53 protein accumulation can indirectly reflect p53 mutation. MDM2 amplification and overexpression might be an early event in the growth of human gliomas.
Assuntos
Neoplasias Encefálicas/genética , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Genes p53/genética , Glioma/genética , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Criança , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
AIM: To detect the expression of calcitonin-gene-related peptide (CGRP), adrenocorticotropin (ACTH), and serotonin (5-HT) in normal human lymph nodes and explore their influences on immune system. METHODS: The expression of CGRP, ACTH and 5-HT in the lymph nodes, including proliferative lymph nodes, were detected by SABC Immunohistochemical staining. RESULTS: In 35 cases of lymph node specimens, the positive rates of CGRP, ACTH and 5-HT expression were 88.5%(31/35), 85.4%(30/35) and 94.2%(33/35) respectively. These 3 molecules had a similar distribution in germinal center of lymph nodes, mainly in the cells of paracortical region, the cells in germinal center of lymph follicles and macrophages, etc. CONCLUSION: There are considerably high positive rates of CGRP, ACTH and 5-HT in human peripheral lymph nodes, and their distribution area are basically coincident with that of immunocytes in the lymph nodes.
