Stefania Scarpino1, Gian Luca Rampioni Vinciguerra1, Arianna Di Napoli1, Flavio Fochetti1, Stefania Uccini1, Daniela Iacono2, Paolo Marchetti2, Luigi Ruco3. 1. Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University, Rome, Italy. 2. Oncology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University, Rome, Italy. 3. Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University, Rome, Italy. Electronic address: luigi.ruco@uniroma1.it.
Abstract
OBJECTIVES: To investigate prevalence and age-distribution of ALK- or ROS1-translocated adenocarcinomas in patients ≤50 years of age. MATERIALS AND METHODS: Paraffin sections of pulmonary adenocarcinoma were analyzed for ALK (637 cases) and ROS1 (376 cases) translocations using FISH, and for EGFR mutations (789 cases) using mutant-specific Real-Time PCR. RESULTS: ALK or ROS1 fusions were detected in 55 of 637 cases (8.6%). When patients were stratified for age, it was found that six of six cases (100%) of lung adenocarcinoma diagnosed in patients <30 years of age were translocated for ALK (4 cases) or ROS1 (2 cases). With the increase of age, there was a gradual decrease in the percentage of positive cases. In fact, ALK-translocated or ROS1-translocated cases were 5 of 17 cases (29%) in the 31-40 years age-group, 6 of 46 cases (13%) in the 41-50 years age-group, and 38 of 568 cases (7.0%) in patients older than 50 years. The six patients <30 years of age (5F/1M), including two pediatric patients (≤18 years old), presented with stage IV disease, were never or light smoker, and had no family history of pulmonary tumours. Four of the six patients, were treated with crizotinib and had an objective response. CONCLUSIONS: Our findings provide evidence that ALK or ROS1 translocations are crucial events in tumourigenesis of pulmonary adenocarcinoma of very young patients, including pediatric patients.
OBJECTIVES: To investigate prevalence and age-distribution of ALK- or ROS1-translocated adenocarcinomas in patients ≤50 years of age. MATERIALS AND METHODS:Paraffin sections of pulmonary adenocarcinoma were analyzed for ALK (637 cases) and ROS1 (376 cases) translocations using FISH, and for EGFR mutations (789 cases) using mutant-specific Real-Time PCR. RESULTS:ALK or ROS1 fusions were detected in 55 of 637 cases (8.6%). When patients were stratified for age, it was found that six of six cases (100%) of lung adenocarcinoma diagnosed in patients <30 years of age were translocated for ALK (4 cases) or ROS1 (2 cases). With the increase of age, there was a gradual decrease in the percentage of positive cases. In fact, ALK-translocated or ROS1-translocated cases were 5 of 17 cases (29%) in the 31-40 years age-group, 6 of 46 cases (13%) in the 41-50 years age-group, and 38 of 568 cases (7.0%) in patients older than 50 years. The six patients <30 years of age (5F/1M), including two pediatric patients (≤18 years old), presented with stage IV disease, were never or light smoker, and had no family history of pulmonary tumours. Four of the six patients, were treated with crizotinib and had an objective response. CONCLUSIONS: Our findings provide evidence that ALK or ROS1 translocations are crucial events in tumourigenesis of pulmonary adenocarcinoma of very young patients, including pediatric patients.
Authors: Cecily P Vaughn; José Luis Costa; Harriet E Feilotter; Rosella Petraroli; Varun Bagai; Anna Maria Rachiglio; Federica Zito Marino; Bastiaan Tops; Henriette M Kurth; Kazuko Sakai; Andrea Mafficini; Roy R L Bastien; Anne Reiman; Delphine Le Corre; Alexander Boag; Susan Crocker; Michel Bihl; Astrid Hirschmann; Aldo Scarpa; José Carlos Machado; Hélène Blons; Orla Sheils; Kelli Bramlett; Marjolijn J L Ligtenberg; Ian A Cree; Nicola Normanno; Kazuto Nishio; Pierre Laurent-Puig Journal: BMC Cancer Date: 2018-08-16 Impact factor: 4.430