Características de pacientes com câncer de pulmão na cidade de Manaus / Characteristics of patients with lung cancer in the city of Manaus, Brazil

OBJETIVO: Analisar as características de pacientes com câncer de pulmão. MÉTODOS: Estudo retrospectivo e descritivo dos pacientes com diagnóstico histopatológico de câncer de pulmão entre 1995 e 2002 em Manaus (AM). Os dados dos pacientes foram coletados nos arquivos médicos de três hospitais. As análises estatísticas foram realizadas, e as curvas de sobrevida geradas a partir do estimador atuarial. RESULTADOS: Dos 352 pacientes selecionados, 262 (74,4 por cento) eram do sexo masculino e 90 (25,6 por cento) do feminino. A média de idade foi de 62 anos. Os seguintes tipos histológicos foram encontrados: carcinoma de células escamosas, 62,8 por cento; adenocarcinoma, 24,7 por cento; carcinoma de pequenas células, 9,1 por cento; e carcinoma de grandes células, 3,4 por cento. Os estádios IIIB e IV foram os mais comuns, com uma frequência de 45 por cento e 21,5 por cento, respectivamente. Da amostra total, 73,4 por cento foram submetidos a tratamento. Desses, 51,4 por cento foram submetidos à radioterapia; 16,6 por cento, à cirurgia; 15,8 por cento, à quimioterapia; e 16,2 por cento, à radioterapia associada à quimioterapia. Os níveis de sobrevida acumulada foram baixos: a sobrevida em três anos foi de 6,5 por cento e a sobrevida em cinco anos foi de 3,5 por cento. CONCLUSÕES: Este grupo de pacientes com câncer de pulmão apresentou uma sobrevida muito pequena, divergindo dos resultados encontrados na literatura. Isto é provavelmente decorrente da dificuldade de acesso ao sistema de saúde especializado e do estágio avançado do diagnóstico.

OBJECTIVE: To analyze the characteristics of patients with lung cancer. METHODS: A retrospective descriptive study of patients receiving a histopathological diagnosis of lung cancer between 1995 and 2002 in the city of Manaus, Brazil. Data were collected from the medical archives of three hospitals. Statistical analyses were carried out, and survival curves were generated by means of an actuarial estimator. RESULTS: Of the 352 patients selected, 262 (74.4 percent) were male and 90 (25.6 percent) were female. The mean age was 62 years. The following histological types were identified: squamous cell carcinoma, 62.8 percent; adenocarcinoma, 24.7 percent; small cell carcinoma, 9.1 percent; and large cell carcinoma, 3.4 percent. The most common stages were stages IIIB and IV, in 45 percent and 21.5 percent, respectively. Of the total sample, 73.4 percent were submitted to treatment. Of these, 51.4 percent underwent radiotherapy; 16.6 percent, surgery; 15.8 percent, chemotherapy; and 16.2 percent, radiotherapy in association with chemotherapy. Cumulative survival rates were low: three-year survival was 6.5 percent, and five-year survival was 3.5 percent. CONCLUSIONS: In this group of patients with lung cancer, survival rates were considerably lower than those reported in the literature. This might be attributable to the limited access to the specialized health care system and the advanced stage of the disease at diagnosis.

Diagnóstico e prognóstico dos tumores pulmonares neuroendócrinos mediante microscopia eletrônica e análise multivariavel de agrupamento / Using electron microscopy and multivariate cluster analysis to determine diagnosis and prognosis in cases of neuroendocrine lung carcinoma

OBJECTIVE: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. METHODS: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. RESULTS: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. CONCLUSIONS: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

OBJETIVO: Estabelecer, com ajuda do microscópio eletrônico, critérios que possibilitem uma diferenciação mais exata entre os quatro tipos maiores de tumores neuroendócrinos pulmonares: tumor carcinóide típico e atípico, carcinoma de grandes células neuroendócrino e carcinoma de pequenas células. MÉTODOS: Todos os tumores foram avaliados morfometricamente e 16 variáveis foram relacionadas com diferenciação das células tumorais; estas variáveis foram analisadas sob microscopia eletrônica com ajuda de um analisador de imagem digital em 27 tumores. A avaliação através da microscopia eletrônica revelou que todos os tumors investigados podiam ser classificados a um dos quarto tipos listados acima. A análise das variáveis morfométricas foi usada para agrupar os tumores em três grandes grupos, os quais foram relacionados à sobrevivência pelas curvas de Kaplan Meier. RESULTADOS: Os três grupos de carcinoma neuroendócrino associaram-se às curvas da sobrevivência, as quais mostraram características ultrastruturais na microscopia eletrônica de significância prognóstica distinta. Os tumores foram contidos em três grupos bem definidos, que representam o espectro da diferenciação neuroendócrina: tumor carcinóide (grupo 1); tumor carcinóide atípico e carcinoma de grandes células neuroendócrino (grupo 2); e carcinoma de pequenas células (grupo 3). O grupo 2 representa um espectro intermediário na carcinogênese neuroendócrina, entre o carcinóide típico e o carcinoma de pequenas células. CONCLUSÕES: Nossos achados confirmam que a microscopia eletrônica é uma ferramenta útil no diagnóstico e prognóstico dos casos de tumores pulmonares.

p53 immunostaining is correlated with reduced survival and is not correlated with gene mutations in resected pulmonary large cell carcinomas

Malignancy of pulmonary large cell carcinomas (LCC) increases from classic LCC through LCC with neuroendocrine morphology (LCCNM) to large cell neuroendocrine carcinomas (LCNEC). However, the histological classification has sometimes proved to be difficult. Because the malignancy of LCC is highly dependent on proteins with functions in the cell cycle, DNA repair, and apoptosis, p53 has been targeted as a potentially useful biological marker. p53 mutations in lung cancers have been shown to result in expression and protein expression also occurs in the absence of mutations. To validate the importance of both p53 protein expression (by immunostaining) and p53 gene mutations in lung LCC (by PCR-single strand conformational polymorphism analysis of exons 5, 6, 7, and 8) and to study their relationships with clinical factors and sub-classification we investigated the correlation of p53 abnormalities in 15 patients with LCC (5 classic LCC, 5 LCNEC, and 5 LCCNM) who had undergone resection with curative intent. Of these patients, 5/15 expressed p53 and none had mutant p53 sequences. There was a negative survival correlation with positive p53 immunostaining (P = 0.05). After adjustment for stage, age, gender, chemotherapy, radiotherapy, and histological subtypes by multivariate analysis, p53 expression had an independent impact on survival. The present study indicates that p53 assessment may provide an objective marker for the prognosis of LCC irrespective of morphological variants and suggests that p53 expression is important for outcome prediction in patients with the early stages of LCC. The results reported here should be considered to be initial results because tumors from only 15 patients were studied: 5 each from LCC, LCNEC and LCCNM. This was due to the rarity of these specific diseases.