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Claudin 18.2 expression in digestive neuroendocrine neoplasms: a clinicopathological study

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Abstract

Background

Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs).

Methods

Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining.

Results

Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%.

Conclusion

The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.

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Data availability statement

All data in this study are included in the published article.

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Funding

This work was supported by Beijing Natural Science Foundation (7232018), National Natural Foundation of China (92259302), Beijing Natural Science Foundation (Z200015) and the Rare Tumor Research Special Project of the National Natural Science Foundation of China (82141104).

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Author notes

  1. Kang Jiang, Fang Cao and Lisha Yin contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China

    K. Jiang, L. Yin, Y. Hu, X. Zhao & Y. Sun

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China

    F. Cao, X. Huang & X. Ma

  3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China

    J. Li

  4. State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China

    M. Lu

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  1. K. Jiang
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Contributions

Conceptualization: YS, and ML; supervision: YS; data curation and analysis: KJ, FC, LSY, YJH, XYZ, XZH, XLM and JL; funding acquisition: YS; original draft: FC, KJ and LSY; review and editing: FC, KJ, LSY, ML and YS; All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to M. Lu or Y. Sun.

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The authors have no conflicts of interest to declare.

Research involving human participants and/or animals

Human samples and clinical data were collected and used in accordance with the principles of the Declaration of Helsinki and approved by the Ethics committee of Peking University Cancer Hospital.

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All participants provided written informed consents, approval number 2023KT98.

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Jiang, K., Cao, F., Yin, L. et al. Claudin 18.2 expression in digestive neuroendocrine neoplasms: a clinicopathological study. J Endocrinol Invest 47, 1251–1260 (2024). https://doi.org/10.1007/s40618-023-02245-7

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