Prevalence and clinical significance of Claudin-3 expression in cancer - a tissue microarray study on 14,966 tumor samples

Q: What is Claudin-3 (CLDN3) and why is it relevant to cancer?

CLDN3 participates in tight-junction formation that regulates intercellular permeability. Altered CLDN3 expression is associated with tumor progression, making it a candidate for cancer-targeting strategies.

Q: How was CLDN3 expression measured and in how many samples?

CLDN3 prevalence was assessed using immunohistochemistry on a tissue microarray containing 14,966 tumor samples across 133 tumor types and subtypes, along with 608 normal tissue samples.

Q: Which cancers showed the highest and lowest CLDN3 staining patterns?

CLDN3 positivity was most common in neuroendocrine neoplasms and in adenocarcinomas, including several female genital tract and breast cancer subtypes. It was less common in squamous cell carcinomas and mainly absent in melanoma, mesenchymal, and hematolymphatic neoplasms.

Sep 21, 2026

Uploaded by Clementine

Claudin-3 (CLDN3) is involved in tight-junction formation and regulates intercellular permeability, and altered CLDN3 expression has been linked to tumor progression across multiple cancers. A tissue microarray containing 14,966 tumor samples from 133 tumor types and subtypes, plus 608 normal tissue samples, was analyzed by immunohistochemistry to quantify CLDN3 prevalence and assess clinical associations. Results show CLDN3 immunostaining in most analyzable tumors with clear subtype-dependent patterns, and reduced CLDN3 levels relate to worse outcomes in renal cell carcinoma.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Tight junctions and claudin biology

Rationale for targeting CLDN3

Büyücek etal. Biomarker Research (2024) 12:154 [https://doi.org/10.1186/s40364-024-00702-w](https://doi.org/10.1186/s40364-024-00702-w) Biomarker Research RESEARCH Open Access Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples Seyma Büyücek 1, Nina Schraps2, Anne Menz1, Florian Lutz 1, Viktoria Chirico1, Florian Viehweger1, David Dum 1, Ria Schlichter1, Andrea Hinsch 1, Christoph Fraune 1,3, Christian Bernreuther 1, Martina Kluth 1, Claudia Hube‑Magg1, Katharina Möller 1, Viktor Reiswich1, Andreas M. Luebke 1, Patrick Lebok1,3, Sören Weidemann1, Guido Sauter1, Maximilian Lennartz 1, Frank Jacobsen1, Till S. Clauditz 1, Andreas H. Marx 1,4, Ronald Simon1*, Stefan Steurer 1, Eike Burandt 1, Natalia Gorbokon1, Sarah Minner 1, Till Krech 1,3 and Morton Freytag1 Abstract Background Claudin‑3 (CLDN3) participates in the formation of the tight‑junctions (TJs) that regulate intercellular permeability. Altered CLDN3 expression has been linked to tumor progression in multiple tumor types. Despite its widespread expression in normal epithelial cells, CLDN3 is considered an attractive drug target candidate, since it maybe more accessible in cancer cells than in normal cells due to their less orchestrated cell growth. Methods To comprehensively determine the prevalence of CLDN3 expression in cancer, a tissue microarray contain‑ ing 14,966 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results CLDN3 immunostaining was observed in 8,479 (68 . 9%) of 12,314 analyzable tumors, including 11. 6% with weak, 6. 2% with moderate, and 51. 1% with strong positivity. CLDN3 staining was found in 96 of 133 tumor cat‑ egories, 80 of which contained at least one strongly positive case. CLDN3 positivity was most seen in neuroendocrine neoplasms (92–100%) and in adenocarcinomas (67–100%), tumors ofthe female genital tract, including various sub‑ types of ovarian and endometrial carcinoma (up to 100%), as well as different subtypes of breast cancer (95 . 3–100%) . CLDN3 positivity was less common in squamous cell carcinomas (0–43 . 2%) and mainly absent in melanoma, mesen‑ chymal, and hematolymphatic neoplasms. In clear cell renal cell carcinoma (ccRCC), low CLDN3 was strongly linked to poor ISUP (p < 0. 0001), Fuhrman (p < 0. 0001), and Thoenes (p < 0. 0001) grades, advanced pT category (p < 0. 0001), high UICC stage (p = 0 . 0006) and distant metastasis (p = 0 . 0011), as well as shortened overall (p = 0 . 0118) and recur‑ rence‑free (p < 0. 0001) survival. In papillary RCC (pRCC), low CLDN3 was associated with poor grade (p < 0. 05), high pT (p = 0 . 0273) and distant metastasis (p = 0 . 0357) . In urothelial carcinoma high CLDN3 was linked to high grade (p < 0. 0001) and nodal metastasis (p = 0 . 0111) . The level of CLDN3 staining was unrelated to parameters of tumor aggressiveness in pancreatic, gastric, and breast cancer. *Correspondence: Ronald Simon [R.Simon@uke.de](R.Simon@uke.de) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thi

FAQs

What is Claudin-3 (CLDN3) and why is it relevant to cancer?

CLDN3 participates in tight-junction formation that regulates intercellular permeability. Altered CLDN3 expression is associated with tumor progression, making it a candidate for cancer-targeting strategies.

How was CLDN3 expression measured and in how many samples?

CLDN3 prevalence was assessed using immunohistochemistry on a tissue microarray containing 14,966 tumor samples across 133 tumor types and subtypes, along with 608 normal tissue samples.

Which cancers showed the highest and lowest CLDN3 staining patterns?

CLDN3 positivity was most common in neuroendocrine neoplasms and in adenocarcinomas, including several female genital tract and breast cancer subtypes. It was less common in squamous cell carcinomas and mainly absent in melanoma, mesenchymal, and hematolymphatic neoplasms.

Sep 21, 2026

Uploaded by Clementine