Original Scientific Articles
Authors
Introduction: Gastric adenocarcinoma is a major cause of global cancer mortality. The HER2 receptor plays a critical role in cell proliferation and survival and is overexpressed or amplified in a subset of gastric cancers, particularly of the intestinal type. The objective of this study was to evaluate HER2 protein expression and gene amplification in gastric adenocarcinoma and determine diagnostic concordance between immunohistochemistry (IHC), chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) methods.
Methods: This retrospective study analyzed 96 patients with histologically confirmed gastric adenocarcinoma who underwent radical surgery (2006-2014). HER2 expression was assessed using IHC and scored according to Hofmann’s system. All tumors with 2+ or 3+ scores were further analyzed for HER2 gene amplification using CISH and FISH. Concordance was evaluated using Cohen’s kappa coefficient.
Results: HER2 expression was negative (score 0 and 1+) in 76.1% of cases, equivocal (2+) in 10.4%, and positive (3+) in 13.5%. All patients with a 3+ score showed HER2 gene amplification using both CISH and FISH. In the 2+ group, amplification was detected in 30% (CISH) and 50% (FISH). Concordance between CISH and FISH was high (κ = 0.78, p < 0.001). HER2 positivity correlated significantly with the intestinal type and was associated with poorer survival, particularly in early-stage tumors.
Conclusion: HER2 is a relevant biomarker in intestinal-type gastric adenocarcinoma. FISH is more sensitive than CISH in equivocal IHC cases. IHC score 3+ can be considered definitive, while FISH is recommended for 2+ cases to confirm gene amplification.
Keywords: gastric adenocarcinoma, HER2, immunohistochemistry, CISH, FISH, gene amplification
How to Cite: Ćuk, M. , Gajanin, R. , Kulić, S. & Vasić Milanović, M. (2025) “The prognostic significance of HER2 in gastric adenocarcinoma”, Biomedicinska istraživanja. 16(2). doi: https://doi.org/10.59137/BII202502507C