RESUMO
Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.
Assuntos
Adenocarcinoma/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Apoptose , Divisão Celular , DNA de Neoplasias/análise , Genes p53/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: The MACIS score uses metastasis, age, completeness of resection, local invasion, and tumor size to stratify patients with papillary thyroid carcinoma (PTC) into four groups with different survival. METHODS: Immunostaining for proliferating cell nuclear antigen (PCNA) was done in 43 cases of PTC. Relationships between proliferative index (percentage of cells that were PCNA positive) and the MACIS parameters were examined. Double staining for PCNA and for silver-stained nucleolar organizer regions (AgNORs, indicating proliferation) was performed in 10 cases. RESULTS: PCNA was detected only in tumor cells. The proliferative index was low (mean, 14.2%; median, 13.0%), did not differ between MACIS groups (p = 0.56), and showed no association with individual MACIS parameters. PCNA immunostaining correlated with AgNOR staining. The mean AgNOR count was 2.28 in PCNA-positive cells and 1.85 in PCNA-negative cells (p
