A consolidated working classification of gastric cancer for histopathologists (Review)

Abstract

Gastric cancer (GC) remains a disease with poor prognosis despite increasing availability of more effective targeted treatment. This may be in part due to the difficulty in selecting patients for appropriate treatment. Conventional taxonomic classifications of GC are ill-suited to make full use of recent advances in personalised therapy. In the past decade a number of molecular classifications have been proposed to address this; however, to date, there has been little implementation in the diagnostic routine. The lack of harmonisation between these classifications, the complexity and unavailability of some of the tests required plus the demands on time and resources, all contribute to poor uptake in the diagnostic routine. In the present study, these classifications were reviewed and an inclusive working classification that includes their main points, focuses on prognosis and treatment options and can be delivered using four on-slide tests ( in situ hybridization for Epstein-Barr encoding region and immunohistochemistry for mismatch repair, E-cadherin and p53) is proposed. These tests can be performed on paraffin-embedded tissue and could be available in the majority of histopathology laboratories. The proposed classification also includes reflex testing for specific biomarkers relevant to treatment selection.

Identification of a unique stress response state of T cells-related gene signature in patients with gastric cancer

“…GC remains a major cancer type with unsatisfactory clinical outcomes, partially due to the failure to optimally utilize the increasingly available targeted and immunological therapies [ 2 ]. Current classification methods, such as the conventional AJCC/UICC-TNM system, do not fully leverage recent advancements in personalized therapies, leaving many patients without the most effective treatment options [ 2 ].…”

“…Globally, gastric cancer (GC) continues to have a high incidence and mortality rate, with more than 1 million new cases diagnosed annually and approximately 784,000 deaths reported in 2018 [ 1 , 2 ]. Although there has been a steady decline in the incidence and mortality rates of gastric cancer in most countries over the past few decades, the number of cases is expected to rise due to aging populations [ 1 ].…”

Implementing an On-Slide Molecular Classification of Gastric Cancer: A Tissue Microarray Study

“…We set out to understand the feasibility of implementing the improved on-slide classification for GC that we proposed [ 10 ]. In particular, we wanted to define the interpretative algorithms for each of the biomarkers used and assess the challenges in interpretation.…”

“…Tumours were given one of six diagnostic categories using a hierarchical approach similar to that used by the WHO classification for endometrial carcinoma [ 14 ] and by others who devised on-slide molecular classifications for GC [ 5 , 6 , 7 , 8 ]. This is described in detail in Costache et al [ 10 ] and summarised in Figure 1 . First, the EBER status was considered, and if positive, the case was classified as GC EBV(+); all GC EBER negative cases were then evaluated for MMR status and, if MMR-deficient, were classified as GC dMMR.…”

“…More importantly, there has been little attention paid to the distinction between diffuse and intestinal subtypes identified by Laurén, which remains a cornerstone of treatment decision-making [ 9 ]. For this reason, we proposed minor modifications [ 10 ], including harmonisation of the nomenclature and biomarkers used, the introduction of an indeterminate category, the addition of the predictive oncology biomarkers currently required for therapy selection and provision for new biomarkers that inevitably will become mandatory [ 11 ]. The inclusion of an indeterminate category was part of the successful implementation of the new molecular classification for endometrial carcinoma [ 12 , 13 , 14 ], and we believe it is an important element for the effective clinical implementation.…”