Abstract
Introduction The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.
Highlights
The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes
We investigated the associations between gastric cancer molecular subtypes, clinicopathological features, and patient’s overall survival
The results showed that diffuse/mixed type of Lauren classification, history of gastrectomy, history of gastric ulcer, TCGA classification (EBV vs. microsatellite unstable (MSI), genomically stable (GS), and chromosomal instability (CIN)), ACRG classification (MSS/EMT vs. MSI, MSS/P53, and MSS/P53+), and integrated classification (EBV vs. MSI, E-cadherin aberrant, P53 aberrant, and P53 normal) were associated with poor prognosis in our population
Summary
The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. These classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). Lauren classification and the WHO classification (2010) are most commonly used, describing intestinal, diffuse, and mixed types in Lauren’s classification and papillary, tubular, mucinous, and poorly cohesive types in WHO classification [4] These classification systems have demonstrated little utility in clinical practice, as they do not have prognostic value and are without therapeutic implications
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