RESUMO
OBJECTIVES: Metastasis to the brain is a severe and common complication in non-small cell lung cancer (NSCLC). The examination of cell cycle associated genes in these lesions may contribute to the understanding of metastatic growths in the central nervous system. The aim of this study was to evaluate the p53, BCL-2 and BAX mRNA and protein expression in NSCLC brain metastases in comparison with matched primary tumors. METHODS: For quantitative TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), fresh frozen tumor specimens from 12 patients with NSCLC brain metastases were available. For immunohistochemical staining, 78 surgically removed NSCLC brain metastases were used. PCR results were analysed using the DeltaDeltaCT method. Staining was analysed using a modified immunoreactive score (IRS). RESULTS: Overall, p53, BCL-2 and BAX expression values in brain metastases and primary tumors showed a wide variety. The comparison of different techniques revealed different findings on the mRNA and protein level. Herein, PCR and ELISA revealed no clear tendencies. In contrast, immunohistochemistry showed significant overexpression of BAX and underexpression of BCL-2 in brain metastases. CONCLUSION: A high variability in the expression of p53, BCL-2 and BAX in NSCLC exists in brain metastases. Immunohistochemistry revealed overexpression of BAX and underexpression of BCL-2 in brain metastases, whereas there were no clear tendencies using PCR and ELISA techniques. More insights into the BAX/BCL-2 interaction are needed before reasonable conclusions can be drawn from the existing data.
Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína Supressora de Tumor p53/análise , Proteína X Associada a bcl-2/análise , Neoplasias Encefálicas/genética , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estatísticas não Paramétricas , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVES: Brain metastases are an increasingly common complication in breast cancer patients. Apoptosis regulating genes are promising candidates for further treatment options. We examined the mRNA and protein expression of p53, BCL-2 and BAX in breast cancer brain metastases versus primary tumors. METHODS: In a two-step approach p53, BCL-2 and BAX mRNA expression in ductal invasive breast cancer brain metastases was examined by: (1) reverse transcription-polymerase chain reaction (RT-PCR) mRNA expression screening (band appearance in relation to an internal standard) and (2) quantitative real-time RT-PCR (CT-values in relation to an internal standard). Protein expression using immunohistochemistry. Results were compared with primary tumors. RESULTS: We found significantly lower BCL-2 mRNA and protein expression in breast cancer brain metastases versus primary tumors. P53 mRNA and protein expression was also lower in metastases. However, this difference was only significant on mRNA but not on the protein level. BAX expression evaluation revealed was contradictory results: mRNA expression was significantly lower whereas protein expression was significantly higher in metastatic lesions. DISCUSSION: The mRNA and protein expression of p53 and BCL-2 seems to be reduced in breast cancer brain metastases. BAX mRNA and protein may be regulated differentially in metastatic lesions.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genéticaRESUMO
Brain metastases are an increasingly frequent complication of cancer. Advances in diagnosis and treatment have led to wider indications for surgery. We present a single-institution series of 177 patients and discuss our results with regard to the literature. Special focus is on patients with advanced age, multiple brain metastases, extracranial metastases, and brain metastasis recurrence. All patients underwent craniotomy for the resection of solid tumor brain metastases between 1994 and 2001 in our department. Perioperative morbidity and mortality as well as survival were evaluated. The median patient age was 59 years (range 32-86 years). In 177 patients, 348 brain metastases were detected, of which 68.0% were supratentorial and 32.0% were infratentorial. According to univariate analysis, the following parameters were significantly associated with prolonged patient survival: (1) age <70 years, (2) one to three intracranial metastases, (3) favorable postoperative performance, (4) resection of all intracranial lesions, and (5) recraniotomy for brain metastasis recurrence. In contrast, the presence of extracranial metastases, metachronous diagnosis, and solitary brain metastases had no influence on survival. As expected, younger age and limited number of brain metastases (up to three) are favorable prognostic factors. Remarkably, the presence of extracranial metastases had no influence on patient survival.