RESUMO
Recent studies from our laboratory suggest that gene-specific methylation changes in sputum could be good intermediate markers for the early detection of lung cancer and defining the efficacy of chemopreventive interventions. The purpose of our study was to determine the prevalence for aberrant promoter methylation of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein (DAP) kinase, and Ras effector homologue (RASSFIA) genes in nonmalignant bronchial epithelial cells from current and former smokers in a hospital-based, case control study of lung cancer. The relationship between loss of heterozygosity, at 9p and p16 methylation in bronchial epithelium and the prevalence for methylation of these four genes in sputum from cancer-free, current and former smokers were also determined. Aberrant promoter methylation of p16 was seen in at least one bronchial epithelial site from 44% of cases and controls. Methylation of the DAP kinase gene was seen in only 1 site from 5 cases and 4 controls, whereas methylation of the RASSFIA was not detected in the bronchial epithelium. Promoter methylation for p16 and DAP kinase was seen as frequently in bronchial epithelium from current smokers as from former smokers. No promoter methylation of these genes was detected in bronchial epithelium from never-smokers. Methylation of the p16 gene was detected in sputum from 23 of 66 controls. DAP kinase gene promoter methylation was also seen in sputum from 16 controls, and 8 of these subjects were positive for p16 methylation. Methylation of the MGMT gene was seen in sputum from 9 controls, whereas RASSFIA promoter methylation was only seen in 2 controls. The correlation between p16 status in the bronchial epithelium obtained from lung lobes that did not contain the primary tumor and the tumor itself was examined. Seventeen of 18 tumors (94%) showed an absolute concordance, being either methylated in the tumor and at least 1 bronchial epithelial site, or unmethylated in both tumor and bronchial epithelium. These results indicate that aberrant promoter hypermethylation of the p16 gene, and to a lesser extent, DAP kinase, occurs frequently in the bronchial epithelium of lung cancer cases and cancer-free controls and persists after smoking cessation. The strong association seen between p16 methylation in the bronchial epithelium and corresponding primary tumor substantiates that inactivation of this gene, although not transforming by itself, is likely permissive for the acquisition of additional genetic and epigenetic changes leading to lung cancer.
Assuntos
Brônquios/fisiologia , Metilação de DNA , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Fumar/genética , Escarro/metabolismo , Proteínas Supressoras de Tumor , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Brônquios/metabolismo , Brônquios/ultraestrutura , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Estudos de Casos e Controles , Células Cultivadas , Cromossomos Humanos Par 9 , Proteínas Quinases Associadas com Morte Celular , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Células Epiteliais/ultraestrutura , Feminino , Genes p16/fisiologia , Humanos , Perda de Heterozigosidade , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , O(6)-Metilguanina-DNA Metiltransferase/genética , Fumar/efeitos adversos , Fumar/metabolismo , Escarro/citologiaRESUMO
A 71-year-old man with duodenal gastrin cell tumor was being evaluated for residual/metastatic disease. Somatostatin receptor scintigraphy (SRS) identified a 2-cm area of focal uptake within the head of the pancreas, consistent with a pancreatic neuroendocrine tumor. Pathological examination did not reveal any malignancy within the pancreas. Instead, the pancreatic head showed pancreatic polypeptide cell hyperplasia. Strong and diffuse immunoreactivity to somatostatin receptor 2A antibody by immunoperoxidase staining confirmed that the lesion correlated with the site of radioactive tracer (Indium-111 pentetreotide) uptake seen on SRS. The current report therefore presents pancreatic polypeptide cell hyperplasia as a new pitfall in SRS.
Assuntos
Neoplasias Duodenais/diagnóstico por imagem , Gastrinoma/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Células Secretoras de Polipeptídeo Pancreático/diagnóstico por imagem , Receptores de Somatostatina/análise , Somatostatina/análogos & derivados , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Neoplasias Duodenais/química , Reações Falso-Positivas , Evolução Fatal , Gastrinoma/química , Humanos , Hiperplasia , Imuno-Histoquímica , Masculino , Pancreatopatias/metabolismo , Neoplasias Pancreáticas/química , Células Secretoras de Polipeptídeo Pancreático/químicaRESUMO
BACKGROUND: Primary mucinous carcinoma of the skin is a rare sweat gland malignancy that is associated with locally aggressive behavior and a high rate of local recurrence following simple excision. OBJECTIVE: A patient with primary mucinous carcinoma of the scalp, which was treated with Mohs micrographic surgery (MMS), is described. METHODS: Case report and literature review. RESULTS: The patient underwent MMS to remove the tumor. Thirty months after the procedure, the patient remains tumor free. CONCLUSION: Simple excision of primary mucinous carcinoma of the skin is associated with a high recurrence rate. Given the low rate of metastasis and characteristic histologic tumor continuity associated with primary mucinous carcinoma of the skin, as well as the tendency for the tumor to involve cosmetically sensitive areas, such as the face and eyelids, MMS appears to represent a preferable treatment alternative for this particular sweat gland tumor. MMS appears to be associated with a very low risk of tumor recurrence.