Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：Claudin18同工型2（CLDN18.2）是胃和胃食管交界（G/GEJ）腺癌的新兴生物标志物和治疗靶标。本研究旨在更深入地了解CLDN18.2阳性模式，预后影响，以及与各种人口统计的联系，临床,G/GEJ腺癌的分子特征。
方法：通过免疫组织化学评估来自美国304例G/GEJ腺癌患者的存档肿瘤组织样本的CLDN18.2阳性。CLDN18.2阳性定义为CLDN18染色强度≥2+的肿瘤细胞≥50%或≥75%。分析CLDN18.2阳性模式与预后和临床病理/人口统计学特征的关系。在可能的情况下,对匹配的组织样品分析CLDN18.2阳性以评估原发性和转移性肿瘤之间的一致性以及化疗前后的一致性。
结果：CLDN18.2阳性肿瘤（临界值≥75％）的总体患病率为44.4％（304中的n=135）。CLDN18.2阳性肿瘤在胃腺癌中的患病率为51.4％（177中的91例），在GEJ腺癌中的患病率为34.6％（127中的44例）。当临界值≥50%时,CLDN18.2阳性肿瘤在胃腺癌中的患病率为64.4%(n=114/177),在GEJ腺癌中为44.9%(n=57/127).使用任一阈值，总生存率与CLDN18.2阳性之间均无关联。CLDN18.2阳性和性别之间有统计学意义的关联，G/GEJ腺癌的组织学类型，和腺癌亚型（≥75%临界值），转移部位和肿瘤分级(≥50%临界值)。CLDN18.2阳性的总体一致性（≥75％的临界值）对于匹配的原发性与转移性肿瘤样品为73％（37个中的27个），对于化疗前后的匹配样品为74％（39个中的29个）。
结论：这项研究表明，CLDN18.2阳性与G/GEJ腺癌的生存率无关，与公布的数据一致。在匹配样本分析的基础上，CLDN18.2似乎证明了作为生物标志物的>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。
方法：通过免疫组织化学评估来自美国304例G/GEJ腺癌患者的存档肿瘤组织样本的CLDN18.2阳性。CLDN18.2阳性定义为CLDN18染色强度≥2+的肿瘤细胞≥50%或≥75%。分析CLDN18.2阳性模式与预后和临床病理/人口统计学特征的关系。在可能的情况下,对匹配的组织样品分析CLDN18.2阳性以评估原发性和转移性肿瘤之间的一致性以及化疗前后的一致性。
结果：CLDN18.2阳性肿瘤（临界值≥75％）的总体患病率为44.4％（304中的n=135）。CLDN18.2阳性肿瘤在胃腺癌中的患病率为51.4％（177中的91例），在GEJ腺癌中的患病率为34.6％（127中的44例）。当临界值≥50%时,CLDN18.2阳性肿瘤在胃腺癌中的患病率为64.4%(n=114/177),在GEJ腺癌中为44.9%(n=57/127).使用任一阈值，总生存率与CLDN18.2阳性之间均无关联。CLDN18.2阳性和性别之间有统计学意义的关联，G/GEJ腺癌的组织学类型，和腺癌亚型（≥75%临界值），转移部位和肿瘤分级(≥50%临界值)。CLDN18.2阳性的总体一致性（≥75％的临界值）对于匹配的原发性与转移性肿瘤样品为73％（37个中的27个），对于化疗前后的匹配样品为74％（39个中的29个）。
结论：这项研究表明，CLDN18.2阳性与G/GEJ腺癌的生存率无关，与公布的数据一致。在匹配样本分析的基础上，CLDN18.2似乎证明了作为生物标志物的>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。
