Gastric Cancer: Applicability and Feasibility of Molecular and Histological Classification in Clinical Practice

Author(s) :

Esmeralda Celia Marginean1,2

1 Baylor College of Medicine, Houston, Texas, USA

2 Baylor St. Luke’s Hospital, Houston, Texas, USA

Corresponding author: Esmeralda Celia Marginean, Email:

Published: Volume I, Issue 2 (December 2021) 8-26, , , - DOI: 10.53011/JMRO.2021.02.02

Open Access

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December 27, 2021 0 Comments


Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer-related deaths in the world. GC is a heterogeneous disease with diverse molecular and histological subtypes, which, may have different therapeutic implications. Using sophisticated molecular technologies and analyses, 3 separate groups recently provided genetic and epigenetic molecular classifications of GC: Singapore-Duke, The Cancer Genome Atlas project (TCGA) and the Asian Cancer Research Group (ACRG). These molecular classifications are time-consuming, complex, and costly and require sophisticated molecular technologies, which, prevent their widespread availability and use in clinical practice. Therefore, several practical pathological classifications were developed using immunohistochemical stains, fluorescent in situ hybridization and/or polymerase chain reaction (PCR), which, approximate, albeit not perfectly, the molecular classifications of GC. These are simple algorithms, less expensive and easy to reproduce in any pathology laboratory. Both molecular and histological classifications should be used for choosing adequate therapy and stratification purposes in clinical trials. This is a review of current molecular and pathological classification of GC.

Fig. 1. Lauren Classification of Gastric Cancer
Fig. 2. HER2 testing in gastric cancer: A. Immunohistochemical staining is interpreted as negative (score 0 and 1+), equivocal (score 2+) and positive (score 3+). Tumors with equivocal (2+) staining should be confirmed by fluorescent in situ hybridization (FISH), which, analyzes the ratio between HER2 gene copy number and chromosome 17 centromere. HER2/CEP17 ratio > 2 in over 20 tumor cells is considered HER2 amplified.
Fig 2B. HER2 scoring guidelines in gastric cancer in biopsy and resection specimens, according to the ToGA trial.
Fig. 3. Practical pathological algorithms that approximate molecular classification of gastric cancer. A. Integrated classification. B. TCGA classification. EBER in situ hybridization separates EBV group; immunohistochemical stains for MMR or PCR separate MSI group; E-cadherin immunohistochemical stain separate genomically stable (GS) group and the remainder are chromosomal instability (CIN) group. C. ACRG classification. Immunohistochemical stains for MMR or PCR separate MSI group; aberrant E-cadherin stain (complete loss or faint cytoplasmic staining) separate MSS/EMT group; aberrant p53 immunostain (strong staining in >70% of tumor cells) separates the MSS/TP53- group; the remainder group with wild-type (normal) p53 staining pattern is MSS/TP53+ group.
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