Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic EventsReportar como inadecuado




Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Birt-Hogg-Dubé syndrome BHD is an inherited disorder caused by genetic mutations in the folliculin FLCN gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas RCCs. Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ n = 2, minimally invasive adenocarcinoma n = 1, papillary adenocarcinoma n = 1, micropapillary adenocarcinoma n = 1, atypical adenomatous hyperplasia n = 8, and micronodular pneumocyte hyperplasia MPH-like lesion n = 1. Five of the six adenocarcinoma-MPH-like lesions 83.3% demonstrated a loss of heterozygosity LOH of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene EGFR and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin p-mTOR and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.



Autor: Mitsuko Furuya , Reiko Tanaka, Koji Okudela, Satoko Nakamura, Hiromu Yoshioka, Toyonori Tsuzuki, Ryo Shibuya, Kazuhiro Yatera, Hi

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados