Background: The Cancer Genome Atlas (TCGA) classified 20% of stomach cancers as genetically stable (GS), aneuploidy, and early-identified, with 73% diffuse subtype enrichment and cadherin-1 (CDH1) somatic mutations. Chromosomally unstable (CIN) stomach malignancies are 50% more prevalent in esophago-gastric junction tumors. Microsatellite instability (MSI) results from DNA mismatch repair errors. The MMR system corrects base mismatches, insertions, and deletions for accurate DNA replication. Lynch syndrome raises young people's risk of colorectal, endometrial, ovarian, and stomach cancer due to autosomal dominant MMR gene mutations. Epstein-Barr virus (EBV) causes breast, lung, stomach, colon, and lung cancers. EBV gene expression and host genome control alter stomach cancer cell cycle pathways and gene expression. EBV-positive gastric tumors (9% of stomach cancers) usually affect men. According to the Asian Cancer Research Group (ACRG), gastric cancer has four molecular classifications: microsatellite stability with epithelial-mesenchymal transition (MSS/EMT), MSS/TP53+ aberrant, which commonly has a higher EBV etiology, and MSS/TP53 normal subgroups; and distal stomach microsatellite instability (MSI).

Aim of the study : We examined  the potential of immunohistochemistry to molecularly classify gastric adenocarcinoma according to (TCGA) and (ACRG) algorithms and genetic classification.

Material and methods : From Baghdad, Iraq, we gathered 40 formalin-fixed paraffin-embedded stomach cancer tissue blocks. Primary gastric adenocarcinoma cases were studied using available clinicopathological data and surgical tissues. The immunohistochemical expression assessed by scoring systems and referenced algorithms was used to molecularly classify the gastric adenocarcinoma cases.

Results: IHC staining for P53 was positive in 26 cases (65%) and negative in 14 (35%). EBV-Latent membrane protein (LMP) immunological staining was positive in 27 (67.5%) and negative in 13 (32.5%) cases. A score of 0 (negative) was found in 2 cases (5%), score 1 in 6 (15%), score 2 in 12 (30%), and score 3 in 20 (50%) of E-Cadherin IHC staining. MSI was positive in 39 (97.5%) and negative in 1 (2.5%). The MLH1/PMS2 heterodimeric couple had 13 positive and 27 negative cases. The MSH2/MSH6 heterodimeric couple was positive at 87.5% and negative at 12.5%. Based on the suggested algorithm for TCGA Group A, 67.5% (27 cases) of the forty patients tested positive for the Epstein-Barr virus. Twelve MSI cases (30% of the samples) were found. No genomically stable cases were observed, indicating 0% of the cases, and one case was referred to as chromosomal instability (2.5%). For (ACRG) Group B, 27 MSI cases (67.5% of the sample) were found, one case classified as MSS/EMT (2.5%), and twelve people (30%) had MSS/aberrant P53. MSS/normal P53 cases were not reported.

Conclusion: Immunohistochemical analysis can be used to distinguish immunophenotypic groups in gastric adenocarcinoma, revealing distinct clinicopathological characteristics. This study demonstrates the classification of gastric adenocarcinoma into biologically and clinically distinct subgroups, facilitating clinical diagnosis.

Keywords: gastric adenocarcinoma, molecular classification , immunohistochemistry , P53 , microsatellite instability.