RESUMO
Neuroendocrine (NE) tumors of the lung represent a wide spectrum of phenotypically distinct entities, with differences in tumor progression and aggressiveness, which include carcinoid tumor (CT) and small-cell lung carcinoma (SCLC). Approximately 20-40% of patients with both typical and atypical CT are non-smokers, while virtually all patients with SCLC are cigarette smokers. Cigarette smoke contains numerous molecules which have been identified as carcinogens. The real impact of nicotine in the development of tumors is not well known. Recent studies show that nicotine upregulates factors of transcription through the nicotinic receptors. The aim of our work was to study the expression of the nicotinic receptors in normal and neoplastic pulmonary NE cells. An immunohistochemical study was carried out with antibodies against NE markers and subunits alpha7 and beta2 of nicotinic receptors in 7 normal lungs, 10 CT (8 typical and 2 atypical) and 10 SCLC fixed in formalin and embedded in paraffin. This study was completed with reverse transcription-polymerase chain reactions (RT-PCR) detection of alpha7-subunit nicotinic receptor mRNA expression. Our data showed that beta2-subunit of nicotinic receptors is never expressed in normal NE cells of lungs and very rarely in NE tumors. In contrast, alpha7-subunit is constantly found in NE cells in normal lungs. In tumors, its expression is significantly higher in SCLC than in CT (p=0.009). Thus, alpha7 subunit nicotinic receptor in a context of chronic nicotinic intoxication seems to be associated with an aggressive phenotype in the spectrum of the NE tumors.
Assuntos
Tumor Carcinoide/metabolismo , Neoplasias Pulmonares/metabolismo , Células Neuroendócrinas/metabolismo , Receptores Nicotínicos/biossíntese , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adulto , Idoso , Tumor Carcinoide/patologia , Feminino , Imunofluorescência , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Pequenas Células do Pulmão/patologia , Fumar/efeitos adversos , Receptor Nicotínico de Acetilcolina alfa7RESUMO
High-risk human papillomaviruses (HPV) are largely implicated in the carcinogenesis of cervical carcinomas. Their role in bronchopulmonary carcinomas is still unclear. In the present study, we have explored 218 fresh frozen lung tumours for the presence of HPV with the Roche line blot assay and for the expression of mRNAs encoding E6 oncoprotein in HPV positive tumours. Only four samples were positive for HPV detection, one poorly differentiated squamous cell carcinoma and three large cell carcinomas. E6 mRNA was undetectable in these four samples. Our data confirm the low prevalence of HPV in lung carcinomas in Western European countries and do not plead in favour of a carcinogenic role for HPV in these carcinomas.
Assuntos
Adenocarcinoma/virologia , Neoplasias Pulmonares/virologia , Pulmão/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adulto , Idoso , Sondas de DNA de HPV , DNA Viral/análise , Feminino , Genótipo , Humanos , Pulmão/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , RNA Mensageiro/metabolismo , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitina-Proteína Ligases/genéticaRESUMO
Aborda metodologia de identificaçäo de fatores de acidente e suas interrelaçöes, localiza fatores de risco e, a partir deles, torna efetiva a prática da prevençäo
