RESUMEN
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.
Asunto(s)
Adenocarcinoma/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Apoptosis , División Celular , ADN de Neoplasias/análisis , Genes p53/genética , Humanos , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-mdm2 , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVES: Lymphoma is the most frequent testicular malignancy in men over 60 years of age. Even though patients present initially with localized disease, the high incidence of bilateral involvement, synchronous or not, and early systemic dissemination are characteristic of these neoplasms. Sometimes the interval between tumor involvement of both testes is long. The question is raised whether either the patient has a predisposition to present new clones of transformed lymphocytes, or the same disease using the same pathway from a systemic reservoir infiltrates the contralateral testis. METHOD: Polymerase chain reaction and DNA sequencing were used to detect immunoglobulin heavy chain (IgH) rearrangement in paraffin-embedded specimens from asynchronous tumors affecting the right and left testis of a 85-year-old man with an interval period of 13 months. RESULTS: Both tumors showed the same IgH rearrangement. CONCLUSIONS: The lymphoma affecting the left and right testis derived from the same clone. It makes a strong case that lymphoma of the testis is the first manifestation of a systemic disease and should be treated aggressively early at the beginning of the disease.