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.

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 can...

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Main Authors: Seyma Büyücek, Florian Viehweger, Viktor Reiswich, Natalia Gorbokon, Viktoria Chirico, Christian Bernreuther, Florian Lutz, Simon Kind, Ria Schlichter, Sören Weidemann, Till S Clauditz, Andrea Hinsch, Ahmed Abdulwahab Bawahab, Frank Jacobsen, Andreas M Luebke, David Dum, Claudia Hube-Magg, Martina Kluth, Katharina Möller, Anne Menz, Andreas H Marx, Till Krech, Patrick Lebok, Christoph Fraune, Guido Sauter, Ronald Simon, Eike Burandt, Sarah Minner, Stefan Steurer, Maximilian Lennartz, Morton Freytag
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0321105
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author Seyma Büyücek
Florian Viehweger
Viktor Reiswich
Natalia Gorbokon
Viktoria Chirico
Christian Bernreuther
Florian Lutz
Simon Kind
Ria Schlichter
Sören Weidemann
Till S Clauditz
Andrea Hinsch
Ahmed Abdulwahab Bawahab
Frank Jacobsen
Andreas M Luebke
David Dum
Claudia Hube-Magg
Martina Kluth
Katharina Möller
Anne Menz
Andreas H Marx
Till Krech
Patrick Lebok
Christoph Fraune
Guido Sauter
Ronald Simon
Eike Burandt
Sarah Minner
Stefan Steurer
Maximilian Lennartz
Morton Freytag
author_facet Seyma Büyücek
Florian Viehweger
Viktor Reiswich
Natalia Gorbokon
Viktoria Chirico
Christian Bernreuther
Florian Lutz
Simon Kind
Ria Schlichter
Sören Weidemann
Till S Clauditz
Andrea Hinsch
Ahmed Abdulwahab Bawahab
Frank Jacobsen
Andreas M Luebke
David Dum
Claudia Hube-Magg
Martina Kluth
Katharina Möller
Anne Menz
Andreas H Marx
Till Krech
Patrick Lebok
Christoph Fraune
Guido Sauter
Ronald Simon
Eike Burandt
Sarah Minner
Stefan Steurer
Maximilian Lennartz
Morton Freytag
author_sort Seyma Büyücek
collection DOAJ
description 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.
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spelling doaj-art-ee75bd2b29fd4103b20445ddb5dd81422025-08-20T02:08:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01204e032110510.1371/journal.pone.0321105Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors.Seyma BüyücekFlorian ViehwegerViktor ReiswichNatalia GorbokonViktoria ChiricoChristian BernreutherFlorian LutzSimon KindRia SchlichterSören WeidemannTill S ClauditzAndrea HinschAhmed Abdulwahab BawahabFrank JacobsenAndreas M LuebkeDavid DumClaudia Hube-MaggMartina KluthKatharina MöllerAnne MenzAndreas H MarxTill KrechPatrick LebokChristoph FrauneGuido SauterRonald SimonEike BurandtSarah MinnerStefan SteurerMaximilian LennartzMorton FreytagOccludin 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.https://doi.org/10.1371/journal.pone.0321105
spellingShingle Seyma Büyücek
Florian Viehweger
Viktor Reiswich
Natalia Gorbokon
Viktoria Chirico
Christian Bernreuther
Florian Lutz
Simon Kind
Ria Schlichter
Sören Weidemann
Till S Clauditz
Andrea Hinsch
Ahmed Abdulwahab Bawahab
Frank Jacobsen
Andreas M Luebke
David Dum
Claudia Hube-Magg
Martina Kluth
Katharina Möller
Anne Menz
Andreas H Marx
Till Krech
Patrick Lebok
Christoph Fraune
Guido Sauter
Ronald Simon
Eike Burandt
Sarah Minner
Stefan Steurer
Maximilian Lennartz
Morton Freytag
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.
PLoS ONE
title 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_short 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.
title_sort 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
url https://doi.org/10.1371/journal.pone.0321105
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