Human Epidermal Growth Factor Receptor 2-Positive, Claudin-18 Isoform 2-Positive, Mismatch Repair-Deficient Gastric Cancer Revealed by Immunohistochemical Analysis of Surgical Specimens: A Case Report.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR) proteins, claudin-18 isoform 2 (CLDN18.2), and the programmed cell death ligand-1 combined positive score (PD-L1 CPS) are predictive biomarkers for the efficacy of combination chemotherapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. However, only a small proportion of these patients are positive for at least two of these predictive biomarkers. CASE: We present a rare case of HER2-positive, CLDN18.2-positive, MMR-deficient gastric cancer. A 72-year-old man was initially diagnosed with clinical stage IVB gastric cancer (cT4aN0, M1 PUL). Immunohistochemical analysis of endoscopic biopsy specimens revealed HER2-negative, CLDN18.2-negative, and MMR-proficient gastric cancer. He underwent surgery to remove the hemorrhagic gastric cancer before chemotherapy, and immunohistochemical analysis of surgical specimens revealed HER2-positive, CLDN18.2-positive, and MMR-deficient gastric cancer. Moreover, a transbronchial lung biopsy after surgery showed that one of the bilateral multiple lung nodules was lung adenocarcinoma, and he was ultimately diagnosed with pathological stage IIB gastric cancer and clinical stage IVB lung cancer. He died of lung cancer without any signs of gastric cancer recurrence during 17 months of follow-up. CONCLUSION: HER2-positive, CLDN18.2-positive, MMR-deficient gastric cancer is extremely rare. Adequate endoscopic biopsy sampling from different areas of a tumor is essential for accurate predictive biomarker assessment in patients with gastric or gastroesophageal junction cancer because of intratumoral heterogeneity.