BIM deletion polymorphisms in hispanic patients with non-small cell lung cancer carriers of EGFR mutations

Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. Results: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). Methods: We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. Conclusions: The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.

• Autores: Cardona-Mendoza, Andrés Felipe; Rojas Puentes, Leonardo; Wills, Beatriz; Arrieta, Oscar; Carranza Isaza, Hernán; Vargas Báez, Carlos Alberto; Otero, Jorge; Corrales-Rodriguez, Luis; Martín, Claudio; Reguart, Noemi; Archila, Pilar; Rodríguez Ariza, July Katherine; Cuello, Mauricio; Ortíz, Carlos; Franco, Sandra; Rolfo, Christian; Rosell, Rafael
• Fecha de publicación: 2016
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/2374
• Acceso en línea: http://hdl.handle.net/20.500.12495/2374; https://doi.org/10.18632/oncotarget.12112
• Palabra clave: Neoplasias pulmonares; Proteína 11 similar a Bcl2; Genes erbB-1; BIM deletion; Non-small cell lung cancer; EGFR mutation; Survival
• License: Attribution 4.0 International