Molecular subtyping of gastric cancer according to ACRG using immunohistochemistry – Correlation with clinical parameters

Gastric cancer (GC) is a very heterogenous disease necessitating further stratification for prognostic and therapeutic aspects. Based on the recommendation of The Asisan Cancer Research Group (ACRG) recently established four molecular subtypes (MSI, MSS/EMT, MSS/TP53+, MSS/TP53-) which require molec...

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Published in:Pathology, research and practice research and practice, 2022-03, Vol.231, p.153797-153797, Article 153797
Main Authors: Pretzsch, Elise, Bösch, Florian, Todorova, Rumyana, Nieß, Hanno, Jacob, Sven, Guba, Markus, Kirchner, Thomas, Werner, Jens, Klauschen, Frederick, Angele, Martin K., Neumann, Jens
Format: Article
Language:English
Subjects:
ACRG
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Chi-Square Distribution
Cohort Studies
EMT
Female
Gastric cancer
Humans
Immunohistochemistry - methods
Immunohistochemistry - statistics & numerical data
Immunophenotyping - methods
Immunophenotyping - statistics & numerical data
Male
Middle Aged
Molecular subtyping
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Tumor budding
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Summary:Gastric cancer (GC) is a very heterogenous disease necessitating further stratification for prognostic and therapeutic aspects. Based on the recommendation of The Asisan Cancer Research Group (ACRG) recently established four molecular subtypes (MSI, MSS/EMT, MSS/TP53+, MSS/TP53-) which require molecular expression analysis. The technology required for comprehensive molecular analysis is expensive and not applicable for routine diagnostics. Thus, in this study we established a classification system utilizing immunohistochemistry and morphology-based analyses as surrogate markers in order to reproduce the ACRG molecular subtypes of gastric cancer. To clarify the clinical relevance of the novel classification system, we performed a correlation with established clinical parameters. The study cohort consisted of 189 patients with GC (UICC III and IV). Using immunohistochemistry, the following markers were analysed: MLH1, MSH2, MSH6, PMS2 (as a surrogate for microsatellite status), p53, SOX9. We assessed tumor budding as a surrogate for EMT to distinguish between MSS/EMT and MSS/non-EMT groups. Immunohistochemical and morphologic subtyping classified cases as follows: 10% MSI, 35% MSS/EMT, 16% MSS/TP53 + and 39% MSS/TP53–. Subtypes significantly correlated with the Lauren classification, tumor stage, venous invasion and SOX9 expression (p 
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2022.153797