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A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability

2020; Multidisciplinary Digital Publishing Institute; Volume: 12; Issue: 7 Linguagem: Inglês

10.3390/cancers12071863

2072-6694

Mauricio P. Pinto, Miguel Córdova-Delgado, Ignacio N. Retamal, Matías Muñoz-Medel, María Loreto Bravo, Doris Durán, Francisco Villanueva, César Sánchez, Francisco Acevedo, Sebastián Mondaca, Érica Koch, Carolina Ibáñez, Héctor Galindo, Jorge Madrid, Bruno Nervi, José Peña, Javiera Torres, Gareth I. Owen, Alejandro H. Corvalán, Ricardo Armisén, Marcelo Garrido,

Gastrointestinal Tumor Research and Treatment

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein-Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53-). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.