Published online Aug 24, 2021. doi: 10.5306/wjco.v12.i8.688
Peer-review started: January 27, 2021
First decision: March 31, 2021
Revised: April 9, 2021
Accepted: July 23, 2021
Article in press: July 23, 2021
Published online: August 24, 2021
Processing time: 208 Days and 1.7 Hours
Molecular classification of gastric cancer (GC) emerged as a promising option to define therapeutic strategies and prognostic subgroups. However, the costs and technical complexity of molecular methodologies remains an obstacle to its adoption. Thus, their clinical significance by other approaches needs further evidence, especially in the western GC.
Although molecular classifications as proposed by The Cancer Genome Atlas (TCGA) Research Network Group and Asian Cancer Research Group (ACRG) subtypes provided a guide for patient stratification and trials of targeted therapy, the clinical utility of these classifications is still limited due to the technical complexity, as indicated by the fact there is little evidence of its application in a real-world setting.
The purpose of this study was to determine the subgroups of molecular classification by immunohistochemistry (IHC) and in situ hybridization (ISH), and to evaluate its characteristics and impact on long-term survival in a Western cohort of GC patients treated with curative intent.
We retrospectively evaluated GC patients who underwent D2-gastrectomy between 2009 and 2016 by tissue microarray. Cases were assessed for microsatellite instability (MSI) status, E-cadherin and p53 expression by IHC and for Epstein-Barr virus (EBV) by ISH. Clinicopathological characteristics and survival of GC were evaluated according to TCGA and ACRG classification system.
A total of 287 GC patients were included. Based on IHC and ISH analysis, 5 profiles were defined as follows: E-cadherin aberrant (9.1%), MSI (20.9%), p53 aberrant (36.6%), EBV positivity (10.5%), and p53 normal (31%), which corresponded to tumors that showed no alteration in other profiles. Flowchart according to the TCGA and ACRG classifications were used to define the subtypes, where clinical and pathological characteristics associated with GC subtypes were evidenced. In both classifications, the MSI group had better survival. While the subtype represented by the loss of e-cadherin expression (subtype GS and microsatellite stable/epithelial to mesenchymal transition) was related to a worse prognosis. The classification proposed by the TCGA was an independent factor associated with survival in patients with GC.
The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis, and is a viable option for use in a clinical setting.
The identification of gastric adenocarcinoma subtypes through techniques available in clinical practice and the development of integrated approaches for diagnostic applications, such as prognosis prediction or response to therapy intervening, emerge as an essential phase toward personalized medicine in GC treatment.