Retrospective Study of Claudin 18 Isoform 2 Prevalence and Prognostic Association in Gastric and Gastroesophageal Junction Adenocarcinoma

• Published in: JCO precision oncology Vol. 8; p. e2300543
• Main Authors: Waters, Rebecca, Sewastjanow-Silva, Matheus, Yamashita, Kohei, Abdelhakeem, Ahmed, Iwata, Kenneth K, Moran, Diarmuid, Elsouda, Dina, Guerrero, Abraham, Pizzi, Melissa, Vicentini, Ernesto Rosa, Shanbhag, Namita, Ta, Anh, Chatterjee, Deyali, Ajani, Jaffer A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2024
• Subjects: Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Claudins; Esophageal Neoplasms - pathology; Esophagogastric Junction - pathology; Female; Humans; Male; Middle Aged; Prevalence; Prognosis; Protein Isoforms; Retrospective Studies; Stomach Neoplasms - epidemiology; Stomach Neoplasms - pathology
• ISSN: 2473-4284
• DOI: 10.1200/PO.23.00543

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.