ABSTRACT
Early diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of dysplasia could greatly improve the outcome of affected patients. For the first time we compared the mutational landscape of non-progressing dysplasia (NPD; n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC biopsies; a total of 90 samples. Using targeted next-generation sequencing identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, FBXW7), and mutations were validated by Sanger sequencing and/or qPCR. Analysis was extended in silico to 530 head and neck (HNSCC) cases using TCGA data. Mutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was the most frequently mutated gene in both PD and NPD cases. With the exception of R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations were located in motif H2 of p53, whereas none of the NPD mutations were. In summary, we propose that the mutational profile of laryngeal dysplasia has utility for the early detection of patients at risk of progression.
Subject(s)
Genetic Predisposition to Disease , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , Mutation , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Adult , Aged , Aged, 80 and over , Alleles , Amino Acid Substitution , Biomarkers, Tumor , Computational Biology/methods , DNA Mutational Analysis , Disease Progression , Female , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Reproducibility of Results , Risk Assessment , Risk FactorsABSTRACT
Introducción y objetivos: La endoscopia intervencionista nos permite actuar sobre la patología del paciente con mínimas molestias, bajos costes y alta eficiencia. Evaluamos la validez de la biopsia por endoscopia flexible en nuestro hospital, en las lesiones sospechosas de malignidad en el espacio rinofaringolaríngeo. Material y método: Estudio retrospectivo de los pacientes con patología sospechosa de malignidad valorados en el periodo 2006-2016 en nuestro centro. Valoramos la eficacia, la tolerancia y número de complicaciones. Calculamos la reducción de costes frente a la laringoscopia directa en quirófano. Comparamos nuestra muestra con otras de características similares descritas en la bibliografía. Resultados: Treinta pacientes fueron estudiados mediante biopsia por endoscopia flexible en ese período. Diecinueve pacientes obtuvieron resultados positivos que permitieron iniciar el tratamiento de su patología. Siete casos, sin evidencia de malignidad, requirieron nueva biopsia bajo anestesia general que confirmó el diagnóstico de carcinoma. Dos muestras descartaron malignidad, dato que se confirmó tras microcirugía de laringe. Un caso mostró inflamación y la lesión se resolvió tras antibioterapia. En un caso la toma de muestra resultó imposible. Obtenemos de esta forma niveles de sensibilidad del 73% con una especificidad del 100%. No se produjeron complicaciones. La reducción de costes en nuestra muestra fue superior al 80%. Conclusiones: La biopsia por endoscopia flexible aporta ventajas sobre la laringoscopia directa que resultan de interés en el diagnóstico de patología oncológica en otorrinolaringología (AU)
Introduction and objectives: Interventional endoscopy allows us to act on the pathology of the patient with minimal discomfort, low costs and high efficiency. We assessed the validity of flexible endoscopic biopsies in our hospital, in lesions suspected of malignancy in the rhino-pharyngo-laryngeal space. Subjects and methods: Retrospective study of patients with a pathology suspected of malignancy assessed between 2006-2016 in our centre. We evaluated the effectiveness, the tolerance and the number of complications. We calculated the cost reduction in comparison with direct laryngoscopy in the operating room. We compared our sample with others of similar characteristics described in the literature. Results: Thirty patients were studied with a flexible endoscopic biopsy during that period. Nineteen patients obtained positive results which allowed them to start treatment for their pathology. Seven cases had no evidence of malignancy and required another biopsy under general anaesthesia, which confirmed the carcinoma diagnosis. Two samples ruled out malignancy which was confirmed by laryngeal microsurgery. One case showed inflammation and the lesion was cured after antibiotherapy. It was impossible to collect the sample in one case. Thus, we obtained sensitivity levels of 73% with a specificity of 100%. There were no complications. The cost reduction in our sample was above 80%. Conclusions: Flexible endoscopic biopsy has advantages over direct laryngoscopy that are relevant in the diagnosis of oncological pathology in otorhinolaryngology (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Otorhinolaryngologic Neoplasms/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Retrospective Studies , Laryngoscopy , Cost-Benefit Analysis , Deglutition Disorders/pathology , Dysphonia/pathology , Early Detection of Cancer/methodsABSTRACT
INTRODUCTION AND OBJECTIVES: Interventional endoscopy allows us to act on the pathology of the patient with minimal discomfort, low costs and high efficiency. We assessed the validity of flexible endoscopic biopsies in our hospital, in lesions suspected of malignancy in the rhino-pharyngo-laryngeal space. SUBJECTS AND METHODS: Retrospective study of patients with a pathology suspected of malignancy assessed between 2006-2016 in our centre. We evaluated the effectiveness, the tolerance and the number of complications. We calculated the cost reduction in comparison with direct laryngoscopy in the operating room. We compared our sample with others of similar characteristics described in the literature. RESULTS: Thirty patients were studied with a flexible endoscopic biopsy during that period. Nineteen patients obtained positive results which allowed them to start treatment for their pathology. Seven cases had no evidence of malignancy and required another biopsy under general anaesthesia, which confirmed the carcinoma diagnosis. Two samples ruled out malignancy which was confirmed by laryngeal microsurgery. One case showed inflammation and the lesion was cured after antibiotherapy. It was impossible to collect the sample in one case. Thus, we obtained sensitivity levels of 73% with a specificity of 100%. There were no complications. The cost reduction in our sample was above 80%. CONCLUSIONS: Flexible endoscopic biopsy has advantages over direct laryngoscopy that are relevant in the diagnosis of oncological pathology in otorhinolaryngology.
