Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC.

Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer-related deaths worldwide. In western countries, more than half of GC patients are diagnosed at advanced stages and 5-year survival rates range between 20-30%. The only curative treatment is surgery, and despite recent advances in oncological therapies, GC prognosis is still poor. The main prognostic tool for patient categorization and treatment selection is the TNM classification, but its limitations are being increasingly recognized. Early recurrences may occur in early-stage disease, and patients at the same stage show heterogeneous outcomes. Thus, there is a need to improve GC stratification and to identify new prognostic factors, which may allow us to select drug-susceptible populations, refine patient grouping for clinical trials and discover new therapeutic targets. Molecular classifications have been developed, but they have not been translated to the clinical practice. On the other hand, histological assessment is cheap and widely available, and it is still a mainstay in the era of molecular medicine. Furthermore, histological features are acquiring new roles as reflectors of the genotype-phenotype correlation, and their potential impact on patient management is currently being analyzed. The aim of this literature review is to provide a modern overview of the histological assessment of GC. In this study, we discuss recent topics on the histological diagnosis of GC, focusing on the current role of Laurén classification and the potential value of new histological features in GC, such as inflammatory infiltration and tumor budding.