Scholarlink

Background <p>CLDN18.2-targeted therapies show promise in HER2-negative, CLDN18.2-positive advanced gastric cancer (GC); however, cutoffs defining CLDN18.2 positivity vary across studies. Tumors with high expression (moderate to strong membranous expression in ≥ 75% of tumor cells) generally exhibit intratumoral homogeneity and a uniform staining pattern, but intratumoral heterogeneity and staining pattern of CLDN18.2 at lower expression thresholds remains unclear. This study investigated intratumoral heterogeneity of CLDN18.2 by comparing inter-block concordance of expression levels and staining patterns in GC.</p> Methods <p>Eighty-six resected GC specimens were retrospectively analyzed using CLDN18.2 immunohistochemistry on two tissue blocks per tumor. CLDN18.2 expression was categorized as high (≥ 75%), intermediate (&lt; 75% and ≥ 40%), or negative (&lt; 40%), and staining patterns as uniform or variable. Inter-block concordance of expression levels and staining patterns and their influence on concordance and outcomes were assessed.</p> Results <p>Overall inter-block concordance of expression levels was high (77%, κ = 0.89). Discordance was substantially higher in intermediate expression tumors (63.5%) than in high (15.5%) or negative (19%) expression tumors. Uniform staining was observed exclusively in high expression tumors, whereas all intermediate expression tumors displayed variable staining (100%). Among high expression tumors, inter-block concordance was substantially higher with uniform staining (98.0%) than with variable staining (71.5%). CLDN18.2 expression and staining pattern heterogeneity were not associated with worse survival.</p> Conclusion <p>Significant intratumoral heterogeneity of CLDN18.2 expression was observed in GC, particularly in intermediate expression tumors; however, this heterogeneity does not affect survival. These results highlight the importance of standardized assessment methods when applying lower thresholds for CLDN18.2-targeted therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Intratumoral heterogeneity of intermediate CLDN18.2 expression in gastric cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月7日

查看全文
  • Yusuke Kawanaka,
  • Chiaki Inagaki,
  • Masaki Okura,
  • Seiichiro Mitani,
  • Naoki Shiraishi,
  • Kazuko Sakai,
  • Kazuto Nishio,
  • Yutaka Kimura,
  • Yasutaka Chiba,
  • Tomoko Wakasa,
  • Hisato Kawakami,
  • Hidetoshi Hayashi

摘要

Background

CLDN18.2-targeted therapies show promise in HER2-negative, CLDN18.2-positive advanced gastric cancer (GC); however, cutoffs defining CLDN18.2 positivity vary across studies. Tumors with high expression (moderate to strong membranous expression in ≥ 75% of tumor cells) generally exhibit intratumoral homogeneity and a uniform staining pattern, but intratumoral heterogeneity and staining pattern of CLDN18.2 at lower expression thresholds remains unclear. This study investigated intratumoral heterogeneity of CLDN18.2 by comparing inter-block concordance of expression levels and staining patterns in GC.

Methods

Eighty-six resected GC specimens were retrospectively analyzed using CLDN18.2 immunohistochemistry on two tissue blocks per tumor. CLDN18.2 expression was categorized as high (≥ 75%), intermediate (< 75% and ≥ 40%), or negative (< 40%), and staining patterns as uniform or variable. Inter-block concordance of expression levels and staining patterns and their influence on concordance and outcomes were assessed.

Results

Overall inter-block concordance of expression levels was high (77%, κ = 0.89). Discordance was substantially higher in intermediate expression tumors (63.5%) than in high (15.5%) or negative (19%) expression tumors. Uniform staining was observed exclusively in high expression tumors, whereas all intermediate expression tumors displayed variable staining (100%). Among high expression tumors, inter-block concordance was substantially higher with uniform staining (98.0%) than with variable staining (71.5%). CLDN18.2 expression and staining pattern heterogeneity were not associated with worse survival.

Conclusion

Significant intratumoral heterogeneity of CLDN18.2 expression was observed in GC, particularly in intermediate expression tumors; however, this heterogeneity does not affect survival. These results highlight the importance of standardized assessment methods when applying lower thresholds for CLDN18.2-targeted therapies.