Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors

Our plain-English summary of Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors, by S. Büyücek, F. Viehweger, V. Reiswich, et al (PloS One, 2025).

The study

• Authors: S. Büyücek, F. Viehweger, V. Reiswich, N. Gorbokon, V. Chirico, C. Bernreuther, F. Lutz, S. Kind, R. Schlichter, S. Weidemann, T.S. Clauditz, A. Hinsch, A.A. Bawahab, F. Jacobsen, A.M. Luebke, D. Dum, C. Hube-Magg, M. Kluth, K. Möller, A. Menz, A.H. Marx, T. Krech, P. Lebok, C. Fraune, G. Sauter, R. Simon, E. Burandt, S. Minner, S. Steurer, M. Lennartz, M. Freytag
• Journal: PloS One
• Published: 2025;20(4):e0321105
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Occludin is a key component of tight junctions. Reduced occludin expression has been linked to cancer progression in individual tumor types, but a comprehensive and standardized analysis across human tumor types is lacking. To study the prevalence and clinical relevance of occludin expression in cancer, a tissue microarray containing 16,870 samples from 148 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Occludin immunostaining was observed in 10,746 (76.6%) of 14,017 analyzable tumors, including 18.9% with weak, 16.2% with moderate, and 41.6% with strong staining intensity. Occludin positivity was found in 134 of 148 tumor categories and was most frequent in adenocarcinomas (37.5-100%) and neuroendocrine neoplasms (67.9-100%), less common in squamous cell carcinomas (23.8-93%) and in malignant mesotheliomas (up to 48.1%), and rare in Non-Hodgkin's lymphomas (1-2%) and most mesenchymal tumors. Reduced occludin staining was linked to adverse tumor features in several tumor types, including colorectal adenocarcinoma (advanced pT stage, p < 0.0001; L1 status, p = 0.0384; absence of microsatellite instability, p < 0.0001), pancreatic adenocarcinoma (advanced pT stage, p = 0.005), clear cell renal cell carcinoma (high ISUP grade, p < 0.0001; advanced pT stage, p < 0.0001; high UICC stage, p < 0.0001; distant metastasis, p = 0.0422; shortened overall or recurrence-free survival, p ≤ 0.0116), papillary renal cell carcinoma (high pT stage, p < 0.0001; high UICC stage, p = 0.0228; distant metastasis, p = 0.0338; shortened recurrence-free survival, p = 0.006), and serous high-grade ovarian cancer (advanced pT stage, p = 0.0133). Occludin staining was unrelated to parameters of tumor aggressiveness in breast, gastric, endometrial, and thyroidal cancer. Our data demonstrate significant levels of occludin expression in many different tumor entities and identify reduced occludin expression as a potentially useful prognostic feature in several tumor entities.

Copyright: © 2025 Büyücek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

In plain English

This laboratory study did not examine asbestos exposure. Pathologists in Germany stained archived tumor samples for occludin, a protein that helps seal cells together. The tissue microarrays held 16,870 primary tumors from 148 tumor types, plus 608 normal tissue samples. Of 14,017 assessable tumors, 10,746 (76.7%) showed occludin staining. Staining was most common in adenocarcinomas and neuroendocrine neoplasms, less common in squamous cell carcinomas and malignant mesotheliomas (up to 48.1%), and rare in non-Hodgkin's lymphomas and most mesenchymal tumors. The 33 epithelioid and 27 biphasic mesotheliomas assessed were listed under lung, pleura and thymus tumors, but no row said pleural or peritoneal. Lower occludin staining was statistically associated with more advanced tumors in colorectal, pancreatic, high-grade serous ovarian, and clear cell and papillary kidney cancers. In both kidney cancer types, the only ones with follow-up data, it was also associated with shorter survival measures. In breast cancers of no special type and in gastric, endometrial and thyroid cancer, occludin was not related to the aggressiveness measures examined. The authors concluded that loss of occludin is a potentially useful prognostic marker in several tumor types.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory immunohistochemistry study of archived tumor and normal tissue samples arranged on tissue microarrays, with comparison against tumor features and, for clear cell and papillary kidney cancers only, patient follow-up
• Who was studied: 16,870 primary tumors from 148 tumor types and subtypes, plus 608 normal tissue samples (8 donors for each of 76 tissue types), from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany; 14,017 tumors were interpretable; clinical data assessed between 2005 and 2022
• Exposure: No asbestos exposure was studied. The measurement was occludin protein staining in tissue. In squamous cell carcinomas, occludin staining was compared with HPV infection status.
• Main results:
  • Across all assessable tumors, occludin staining was seen in 10,746 (76.7%) of 14,017
  • Occludin positivity was most frequent in adenocarcinomas and neuroendocrine neoplasms, and less frequent in squamous cell carcinomas and malignant mesotheliomas (up to 48.1%)
  • Epithelioid mesothelioma: 40 on the array, 33 assessable, 63.6% negative. Biphasic mesothelioma: 29 on the array, 27 assessable, 51.9% negative. Both are listed in Table 1 under tumors of the lung, pleura and thymus.
  • In colorectal adenocarcinoma, reduced occludin staining was associated with advanced pT stage (p < 0.0001), L1 status (p = 0.0384) and absence of microsatellite instability (p < 0.0001)
  • In clear cell renal cell carcinoma, low occludin staining was linked to shortened overall survival (p = 0.0166) and recurrence-free survival (p = 0.0045), as well as to poor grade, advanced stage and distant metastasis
  • In papillary renal cell carcinoma, low occludin staining was associated with high pT stage (p < 0.0001), high UICC stage (p = 0.0228), distant metastasis (p = 0.0338) and shortened recurrence-free survival (p = 0.006)
  • In ductal adenocarcinoma of the pancreas (p = 0.005) and high-grade serous ovarian cancer (p = 0.0133), low occludin staining was associated with advanced pT stage
  • In a mixed group of squamous cell carcinomas from 9 sites of origin, low occludin expression was associated with absence of HPV infection (p = 0.0001 in the text)
  • Occludin staining was unrelated to parameters of tumor aggressiveness in breast cancers of no special type, gastric, endometrial and thyroid cancer
• The authors' conclusion: The authors concluded that their data show occludin expression in many tumor types and identify loss of occludin expression as a potentially useful prognostic marker in several tumor types
• Limitations the authors state:
  • Antibody validation was limited to comparison with a second antibody, because comparison with another expression method was considered impractical
  • For Hodgkin's lymphoma, Ewing sarcoma, leiomyosarcoma and osteosarcoma, too few tumors were analyzed to judge the clinical significance of elevated occludin

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Immunohistochemistry, Adenocarcinoma, Neoplasm, Squamous Cell Carcinoma, Mesothelioma, Mesenchymal Tumor, Microsatellite Instability (MSI-H).

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