Claudin 18 亚型 2 (CLDN18.2) 是胃和胃食管交界处 (G/GEJ) 腺癌的新兴生物标志物和治疗靶点。本研究旨在更深入地了解 CLDN18.2 阳性模式、预后意义以及与 G/GEJ 腺癌的各种人口、临床和分子特征的关联。来自美国 304 名 G/GEJ 腺癌患者的存档肿瘤组织样本通过免疫组织化学评估 CLDN18.2 阳性。 CLDN18.2阳性定义为≥50%或≥75%的肿瘤细胞CLDN18染色强度≥2。分析了 CLDN18.2 阳性模式与预后和临床病理/人口统计学特征的关联。在可能的情况下，对匹配的组织样本进行 CLDN18.2 阳性分析，以评估原发性肿瘤和转移性肿瘤之间的一致性以及化疗前后的一致性。CLDN18.2 阳性肿瘤的总体患病率（截止值≥75%）为 44.4%（n = 304 中的 135）。 CLDN18.2 阳性肿瘤在胃癌中的患病率为 51.4%（n = 177 例中的 91 例），在 GEJ 腺癌中的患病率为 34.6%（n = 127 例中的 44 例）。截止值≥50%时，胃腺癌中 CLDN18.2 阳性肿瘤的患病率为 64.4%（177 例中的 114 例），GEJ 腺癌中的 CLDN18.2 阳性肿瘤的患病率为 44.9%（127 例中的 57 例）。使用任一阈值时，总生存率与 CLDN18.2 阳性之间没有关联。 CLDN18.2 阳性与性别、G/GEJ 腺癌的组织学类型、腺癌亚型（≥75% 截止值）以及转移部位和肿瘤分级（≥50% 截止值）之间存在统计学显着相关性。匹配的原发性肿瘤与转移性肿瘤样本的 CLDN18.2 阳性率（≥75% 截止值）的总体一致性为 73%（37 例中的 27 例），化疗前后匹配的样本的 CLDN18.2 阳性率为 74%（39 例中的 29 例）。这项研究表明，CLDN18 .2 阳性与 G/GEJ 腺癌的生存率无关，与已发表的数据一致。根据匹配样本分析，CLDN18.2 作为生物标志物似乎表现出 >70% 的一致性。观察到的与某些患者/肿瘤特征的相关性值得进一步研究。

Claudin 18 isoform 2 (CLDN18.2) is an emerging biomarker and therapeutic target in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. This study aimed to obtain deeper understanding of CLDN18.2 positivity patterns, prognostic implications, and associations with various demographic, clinical, and molecular characteristics in G/GEJ adenocarcinoma.Archived tumor tissue samples from 304 patients with G/GEJ adenocarcinoma in the United States were assessed for CLDN18.2 positivity by immunohistochemistry. CLDN18.2 positivity was defined as ≥50% or ≥75% of tumor cells with CLDN18 staining intensity ≥2+. CLDN18.2 positivity patterns were analyzed for association with prognosis and clinicopathologic/demographic characteristics. Where possible, CLDN18.2 positivity was analyzed for matched tissue samples to assess concordance between primary and metastatic tumors and concordance before and after chemotherapy.The overall prevalence of CLDN18.2-positive tumors (with ≥75% cutoff) was 44.4% (n = 135 of 304). CLDN18.2-positive tumors had a prevalence of 51.4% (n = 91 of 177) in gastric and 34.6% (n = 44 of 127) in GEJ adenocarcinoma. With a ≥50% cutoff, the prevalence of CLDN18.2-positive tumors was 64.4% (n = 114 of 177) in gastric adenocarcinoma and 44.9% (n = 57 of 127) in GEJ adenocarcinoma. There was no association between overall survival and CLDN18.2 positivity using either threshold. Statistically significant associations were noted between CLDN18.2 positivity and sex, histologic type of G/GEJ adenocarcinoma, and adenocarcinoma subtype (≥75% cutoff), and metastasis site and tumor grade (≥50% cutoff). The overall concordance of CLDN18.2 positivity (≥75% cutoff) was 73% (27 of 37) for matched primary versus metastatic tumor samples and 74% (29 of 39) for matched samples before and after chemotherapy.This study demonstrated that CLDN18.2 positivity did not correlate with survival in G/GEJ adenocarcinoma, consistent with published data. On the basis of matched sample analysis, CLDN18.2 appears to demonstrate >70% concordance as a biomarker. Observed correlations with certain patient/tumor characteristics warrant further study.