RESUMO
The primary objective of this study is to identify prognostic site-specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter. Paraffin-embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation. Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing. Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated. Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p = 0.006 and p = 0.029, respectively). Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p = 0.020). In univariate analysis, hypermethylation of RASSF1 at CpG sites -53 and -48 and PTEN at CpG site -1310 were the significantly associated with shorter TTR (p = 0.002 and p < 0.000, respectively). Hypermethylation of PTEN at -1310 and DAPK at -1482 were most significantly associated with outcome in multivariate analysis. These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Neoplasias Pulmonares/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Supressoras de Tumor/genética , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Antígenos CD , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos de Casos e Controles , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas Quinases Associadas com Morte Celular , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas/genética , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We report outcomes on 23 patients with oligometastastic (1 or 2 sites) NSCLC treated with aggressive local, regional, and systemic treatment. The results suggest that this is a favorable subset of patients who may benefit from such an approach, with a 22% rate of long-term survival. This treatment strategy is a departure from the usual practice of palliative-only therapy for all NSCLC patients presenting with metastatic disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada/métodos , Neoplasias Pulmonares/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do TratamentoRESUMO
Colon interposition for benign stricture is associated with significant perioperative complications that carry high morbidity and mortality, but long-term sequelae such as further strictures and colonic redundancy are often well-tolerated. These benign complications are frequently described in literature, but adenocarcinoma in the colonic graft is a rare complication. We describe a 60-year-old man with a history of benign esophageal stricture who was treated with colon interposition 40 years ago and presented with dysphagia secondary to stage 1 colon graft adenocarcinoma. He was successfully treated with an Ivor Lewis esophagectomy and primary esophagogastric anastomosis.