Kwak Yoonjin, Kim Tae-Yong, Nam Soo Kyung, Hwang Hye Jung, Han Daeyoung, Oh Hyeon Jeong, Kong Seong-Ho, Park Do Joong, Oh Do-Youn, Lee Hyuk-Joon, Im Seock-Ah, Yang Han-Kwang, Lee Hye Seung
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Oncologist. 2025 Feb 6;30(2). doi: 10.1093/oncolo/oyae238.
Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers.
We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features.
CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P < .001), but there was no correlation with age, sex, or stage (P > .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P < .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival.
This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.
Claudin 18.2（CLDN18.2）是胃癌（GC）靶向治疗的一个有前景的靶点。本研究调查了II-IV期GC或胃食管交界（GEJ）腺癌患者中CLDN18.2表达的发生率及其与临床病理特征和其他关键GC生物标志物的相关性。
我们纳入了1000例接受手术治疗后被诊断为II-IV期GC的患者。进行了CLDN18（43-14A克隆）、PD-L1（22C3 pharmDx）、HER2和FGFR2的免疫组织化学检测。CLDN18.2阳性定义为≥75%的肿瘤细胞中出现中度至强（2+/3+）膜染色。将CLDN18.2表达与生物标志物表达、爱泼斯坦-巴尔病毒（EBV）关联和微卫星不稳定性状态以及临床病理特征进行比较。
34.4%的患者CLDN18.2呈阳性。CLDN18.2阳性在胃中上部三分之一处显著高于胃下部三分之一处（P <.001），但与年龄、性别或分期无关（P >.05）。CLDN18.2阳性在黏液腺癌中罕见（2.8%），但在大多数伴有淋巴间质的胃癌中常见（90.9%）。CLDN18.2阳性在EBV相关的GC（P <.001）和PD-L1阳性（PD-L1 CPS≥5）的GC中较高（P =.014），但在HER2阳性的GC中较低（P =.005）。CLDN18.2阳性与总生存期和无病生存期无显著相关性。
本研究全面评估了韩国II-IV期GC患者的CLDN18.2状态及其与临床病理特征和关键生物标志物的相关性。它可能对指导未来药物开发、扩大治疗选择以及最终改善GC患者的预后具有重要价值。
