RESUMO
BACKGROUND: The U.S. Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating. Previous studies that compared FISH and IHC considered FISH the gold standard, but none compared data with the results of next-generation sequencing (NGS) analysis. MATERIALS AND METHODS: We studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance. RESULTS: Of 51 patients, 4 were positive with FISH (7.8%), and 8 were positive with IHC (15.7%). Three were positive with both. NGS confirmed that four of the five patients who were positive with IHC and negative with FISH were positive for ALK. Two were treated by crizotinib, with progression-free survival of 18 and 6 months. Considering NGS as the most accurate test, the sensitivity and specificity were 42.9% and 97.7%, respectively, for FISH and 100% and 97.7%, respectively, for IHC. CONCLUSION: The FISH-based method of detecting EML4-ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. Screening for EML4-ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. Two patients who were negative with FISH and positive with IHC were treated with crizotinib and responded to therapy.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Rearranjo Gênico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Programas de Rastreamento/métodos , Proteínas de Fusão Oncogênica/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Taxa de SobrevidaRESUMO
BACKGROUND: Many centers routinely culture bronchoscopy samples for mycobacteria even when tuberculosis (TB) is not strongly suspected. The value of this practice has hardly been investigated. OBJECTIVE: The aim of this retrospective study was to assess the utility of routine culture of bronchoscopy samples of lung masses for mycobacteria in a region where TB is not endemic. PATIENTS AND METHODS: The study group consisted of 168 patients who underwent bronchoscopy for investigation of lung masses in a major tertiary-care, university-affiliated facility in central Israel. The findings on acid-fast bacillus staining and culture were reviewed, and data on demographic characteristics were collected from the files. RESULTS: There were 97 men (58%) and 71 women with a mean age of 62 +/- 25 years. One culture (0.6%) grew Mycobacterium tuberculosis. There were no cases of positive acid-fast bacillus smear or positive nontuberculous mycobacteria culture. Sixty USD (5.45%) would be saved per patient without clinical suspicion of TB. CONCLUSIONS: These findings highlight the need to formulate new guidelines for the performance of mycobacterial cultures of bronchoscopy specimens in areas with a low prevalence of TB.