Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples
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 con...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s40364-024-00702-w |
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| author | Seyma Büyücek Nina Schraps Anne Menz Florian Lutz Viktoria Chirico Florian Viehweger David Dum Ria Schlichter Andrea Hinsch Christoph Fraune Christian Bernreuther Martina Kluth Claudia Hube-Magg Katharina Möller Viktor Reiswich Andreas M. Luebke Patrick Lebok Sören Weidemann Guido Sauter Maximilian Lennartz Frank Jacobsen Till S. Clauditz Andreas H. Marx Ronald Simon Stefan Steurer Eike Burandt Natalia Gorbokon Sarah Minner Till Krech Morton Freytag |
| author_facet | Seyma Büyücek Nina Schraps Anne Menz Florian Lutz Viktoria Chirico Florian Viehweger David Dum Ria Schlichter Andrea Hinsch Christoph Fraune Christian Bernreuther Martina Kluth Claudia Hube-Magg Katharina Möller Viktor Reiswich Andreas M. Luebke Patrick Lebok Sören Weidemann Guido Sauter Maximilian Lennartz Frank Jacobsen Till S. Clauditz Andreas H. Marx Ronald Simon Stefan Steurer Eike Burandt Natalia Gorbokon Sarah Minner Till Krech Morton Freytag |
| author_sort | Seyma Büyücek |
| collection | DOAJ |
| description | 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 may be 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 containing 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 categories, 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 of the female genital tract, including various subtypes 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, mesenchymal, 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 recurrence-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. Conclusion In conclusion, our data demonstrate significant levels of CLDN3 expression in many different tumor entities and identify reduced CLDN3 expression as a potential prognostic marker in RCC. |
| format | Article |
| id | doaj-art-29aab683632e4490aaaf89e2dde1d4cb |
| institution | Kabale University |
| issn | 2050-7771 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-29aab683632e4490aaaf89e2dde1d4cb2024-12-15T12:10:46ZengBMCBiomarker Research2050-77712024-12-0112111710.1186/s40364-024-00702-wPrevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samplesSeyma Büyücek0Nina Schraps1Anne Menz2Florian Lutz3Viktoria Chirico4Florian Viehweger5David Dum6Ria Schlichter7Andrea Hinsch8Christoph Fraune9Christian Bernreuther10Martina Kluth11Claudia Hube-Magg12Katharina Möller13Viktor Reiswich14Andreas M. Luebke15Patrick Lebok16Sören Weidemann17Guido Sauter18Maximilian Lennartz19Frank Jacobsen20Till S. Clauditz21Andreas H. Marx22Ronald Simon23Stefan Steurer24Eike Burandt25Natalia Gorbokon26Sarah Minner27Till Krech28Morton Freytag29Institute of Pathology, University Medical Center Hamburg-EppendorfGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfAbstract 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 may be 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 containing 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 categories, 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 of the female genital tract, including various subtypes 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, mesenchymal, 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 recurrence-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. Conclusion In conclusion, our data demonstrate significant levels of CLDN3 expression in many different tumor entities and identify reduced CLDN3 expression as a potential prognostic marker in RCC.https://doi.org/10.1186/s40364-024-00702-wCLDN3Tissue microarrayCancerRenal cell carcinomaBiomarker |
| spellingShingle | Seyma Büyücek Nina Schraps Anne Menz Florian Lutz Viktoria Chirico Florian Viehweger David Dum Ria Schlichter Andrea Hinsch Christoph Fraune Christian Bernreuther Martina Kluth Claudia Hube-Magg Katharina Möller Viktor Reiswich Andreas M. Luebke Patrick Lebok Sören Weidemann Guido Sauter Maximilian Lennartz Frank Jacobsen Till S. Clauditz Andreas H. Marx Ronald Simon Stefan Steurer Eike Burandt Natalia Gorbokon Sarah Minner Till Krech Morton Freytag Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples Biomarker Research CLDN3 Tissue microarray Cancer Renal cell carcinoma Biomarker |
| title | Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples |
| title_full | Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples |
| title_fullStr | Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples |
| title_full_unstemmed | Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples |
| title_short | Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples |
| title_sort | prevalence and clinical significance of claudin 3 expression in cancer a tissue microarray study on 14 966 tumor samples |
| topic | CLDN3 Tissue microarray Cancer Renal cell carcinoma Biomarker |
| url | https://doi.org/10.1186/s40364-024-00702-w |
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