Transformation into large-cell neuroendocrine carcinoma associated with acquired resistance to erlotinib in nonsmall cell lung cancer

No abstract available.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Detecção de micrometástases em câncer de pulmão não-pequenas células estádio pN0: um método alternativo combinando imunohistoquímica e análise em microsséries / Detection of micrometastases in pN0 non-small cell lung cancer: an alternative method combining tissue microarray and immunohistochemistry

OBJETIVO: Apresentar um método alternativo para detectar micrometástases em linfonodos previamente negativos para câncer de pulmão não-pequenas células (CPNPC) pela coloração de rotina com hematoxilina-eosina. MÉTODOS: Setenta e sete linfonodos hilares e mediastinais ressecados de 18 pacientes portadores de CPNPC foram investigados para a presença de micrometástases associando-se análise em microsséries e imunoistoquímica. RESULTADOS: Micrometástases foram detectadas após a identificação de células neoplásicas citoqueratina e cromogranina positivas em microsséries de linfonodos. Dos 18 pacientes inicialmente estadiados como pN0 pela coloração de rotina com hematoxilina-eosina, 9 (50 por cento) foram reestadiados como N1, e o prognóstico foi reavaliado em função de parâmetros histológicos e clínicos. A comparação das curvas de sobrevida mostrou que os pacientes sem micrometástases tiveram maior sobrevida do que os portadores de micrometástases. Além disso, após a análise multivariada controlada para idade, sexo, tipo histológico e reestadiamento, a presença de micrometástases mostrou-se como um fator independente na sobrevida. Entre os pacientes que haviam sido previamente estadiados como pN0, o risco de morte mostrou-se 7 vezes maior para os que foram posteriormente diagnosticados com micrometástases do que para aqueles nos quais não foram identificadas micrometástases. CONCLUSÃO: A combinação da análise em microsséries com a imunoistoquímica pode representar um método alternativo de baixo custo e menos demorado para identificar metástases ocultas e prever o prognóstico em pacientes portadores de CPNPC pN0 cujos tumores foram cirurgicamente ressecados. São necessários estudos prospectivos randomizados com casuísticas maiores para determinar a acurácia desse método alternativo.

OBJECTIVE: To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining. METHODS: A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry. RESULTS: Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50 percent) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified. CONCLUSION: The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.

Epidermal Growth Factor Receptor (EGFR) Expression in Operable Non-small Cell Lung Carcinoma

This study was performed to assay the expression of epidermal growth factor receptor (EGFR) in non-small cell lung carcinoma (NSCLC), and to investigate the relationship between EGFR status and various clinicopathologic features of NSCLC, including angiogenesis and proliferative activity. The expression of EGFR, microvessel count (MVC) measured by CD31 monoclonal antibody, and proliferative activity using Ki-67 labeling index were immunohistochemically analyzed in formalin-fixed and paraffin-embedded tissue specimens from 65 patients with completely resected stage II-IIIA NSCLC. Pathologic and clinical records of all patients were retrospectively reviewed. EGFR was expressed in 18 (28%) of 65 NSCLC samples. More squamous tumors (35%) were EGFR-positive than other NSCLCs (23%) (p-value 0.308). There was a statistically significant correlation between EGFR expression and Ki-67 labeling index (p-value 0.042), but no correlation was observed between EGFR expression and tumor histology, stage, or MVC. There were no differences between EGFR positive and negative tumors in 5-yr disease-free survival (60% vs. 52%, p-value 0.5566) and 5-yr overall survival (53% vs. 45%, p-value 0.3382) rates. In conclusion, our findings suggest that NSCLC proliferative activity may be dependent on EGFR expression, but that EGFR expression had no significant impact on survival in curatively resected NSCLC.

The role of E-cadherin expression in non-small cell lung cancer

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p>0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (> or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.