RESUMEN
BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour that is etiologically related to professional exposure to wood dust and exhibits a poor prognosis. Treatment alternatives to surgery and radiotherapy are needed and may be found in anti-EGFR agents. EGFR gene copy number gains and KRAS/BRAF mutations have been reported to act as positive and negative predictors, respectively, of therapeutic response to EGFR targeted therapies in colorectal adenocarcinoma, a tumour type claimed to be genetically similar to ITAC. Therefore, the aim of this study was to evaluate the occurrence and consequence of EGFR alterations and KRAS and BRAF mutations in a large series of ITAC. METHODS: EGFR protein expression was studied in 98 paraffin embedded tissue samples, organized in a tissue microarray. Gene copy number analysis was performed by FISH using the same tissue microarray, complemented by microarray CGH and MLPA analysis on DNA extracted from 65 fresh frozen tissues. Mutations in EGFR, KRAS and BRAF were analysed by direct sequencing on 65 fresh frozen tissues. RESULTS: EGFR gene copy number gains were observed in 45 %, and protein over-expression in 21 % of the cases. No mutations were found in EGFR or BRAF, while KRAS mutations were present in 12 % of the cases. Neither protein overexpression nor gene copy number gain correlated to histological subtype, tumour stage or clinical follow-up. CONCLUSION: In the largest series of ITAC published to date, and using a number of different techniques, EGFR alterations were frequently observed. Although apparently not useful as a prognostic factor, there may be a basis for investigating EGFR targeted therapies in this group of patients, especially because negative response predictors such as KRAS and BRAF mutations are infrequent or absent, respectively.
Asunto(s)
Adenocarcinoma/genética , Receptores ErbB/genética , Mutación , Neoplasias Nasales/genética , Senos Paranasales/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , Femenino , Dosificación de Gen , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasias Nasales/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas p21(ras) , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Sinonasal squamous cell carcinomas (SCCs) are rare tumors with no etiologic link to tobacco and alcohol, as opposed to other SCCs of the head and neck (HNSCC). Little is known about the genetic changes in sinonasal SCC. METHODS: DNA copy number changes of sinonasal SCC were analyzed by multiplex ligation-dependent probe amplification (MLPA) and microarray comparative genomic hybridization (maCGH), and results were related to clinicopathologic features. RESULTS: Copy number losses most frequently included genes at 9p21, 13q14, 17p13, 17q21, and 18q11. Frequent gains were observed on 8q24, 11q13, 17q12, 19p13, and 20q11-q13. CONCLUSION: The genomic profile of sinonasal SCC showed a number of chromosomal regions with copy number changes similar to those known in HNSCC, in spite of the differences in etiology.