Abstract
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
Highlights
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer death [1]
A Molecular Subtype Classification for GC Based on chromogenic in situ hybridization (CISH)/IHC
We sought to define a molecular classification following some of the criteria defined by The Cancer Genome Atlas (TCGA) [12] and the Asian Cancer Research Group (ACRG) [13]
Summary
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer death [1]. Several studies demonstrate GC is a highly heterogeneous disease [2]. This applies to geographic incidence and mortality rates [3,4] and to clinical and pathological features [5]. Investigators have sought to define a classification system for GC. Initial studies by Lauren classified tumors according to their histopathological and morphological features and divided. GCs into intestinal or diffuse type, or mixed/undefined [6]. Diffuse GCs are associated to poorer prognosis and response to treatments versus intestinal type [7].
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