RESUMEN
BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor. Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib. The purpose of this study was to evaluate the percentage and the pattern of ALK-rearranged cells, the variation in the native ALK copy number, as well as ALK, c-MET and ROS1 protein expression, and their significance on outcome of crizotinib-treated lung adenocarcinoma patients. PATIENTS AND METHODS: Consecutive lung adenocarcinoma specimens (n = 176) 'double-negative' (wild-type EGFR and KRAS) were tested for ALK rearrangements/copy number alterations and for ALK, c-MET and ROS1 protein expression using automated standardized protocols. Preliminary data on the outcome of crizotinib-treated patients were recorded. RESULTS: FISH analysis identified 26/176 (15%) cases with ALK rearrangements. Seven cases had discordant results between the ALK FISH and IHC. Five cases with discordant FISH-positive/IHC-negative revealed FISH 'borderline' positivity (15%-20%). Three cases overexpressed c-MET and responded to crizotinib, and two cases with ALK-'borderline' rearranged cells only, not associated with c-MET expression, progressed under crizotinib. Two cases with discordant FISH-negative/IHC-positive revealed ALK gene amplification without associated c-MET or ROS1 protein expression. CONCLUSIONS: The discrepancies observed between the IHC and FISH data revealed unexpected biological events, rather than technical issues, which potentially can have a strong impact on the therapeutic strategy with crizotinib.
Asunto(s)
Adenocarcinoma/genética , Técnica del Anticuerpo Fluorescente/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/análisis , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma del Pulmón , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Crizotinib , Femenino , Dosificación de Gen/genética , Reordenamiento Génico , Variación Genética/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/análisis , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-met/análisis , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
In recent years, the incidence of oral opportunistic infections has increased, partly due to the widespread implementation of organ and bone marrow transplantation and the increase in the prevalence of human immunodeficiency virus (HIV) infection. Cytology can be used as a rapid, inexpensive and simple routine procedure in diagnosing infectious diseases of the mouth. Moreover, ancillary methods can be applied to cytological samples, increasing the specificity and sensitivity for the diagnosis of infectious diseases. This review describes the cytopathological features of the main viral, fungal, bacterial and parasitic infections of the mouth. Cytological techniques of specimen collection, identification of infectious agents by cytomorphological approaches and ancillary methods, and diagnostic pitfalls will be discussed.