Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance

Our plain-English summary of Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance, by M.V. Dos Santos, A. Holth, K. Bischof, et al (Clinical & Experimental Metastasis, 2024).

The study

• Authors: M.V. Dos Santos, A. Holth, K. Bischof, B. Davidson
• Journal: Clinical & Experimental Metastasis
• Published: 2024;41(1):69-76
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The objective of this study was to analyze the expression and prognostic role of the tight junction protein occludin in high-grade serous carcinoma (HGSC). Occludin protein expression by immunohistochemistry was analyzed in 602 HGSC (417 effusions, 185 surgical specimens). Expression in mesothelioma (n = 87; 45 effusions, 42 surgical specimens) was studied for comparative purposes. Occludin protein expression was found in 587/602 (98%) HGSC vs. 40/87 (46%) mesotheliomas and was predominantly limited to < 5% of cells in the latter (p < 0.001). Occludin was additionally overexpressed in HGSC effusions compared to surgical specimens (p < 0.001) and was overexpressed in post-chemotherapy effusions compared to chemo-naive effusions tapped at diagnosis (p = 0.015). Occludin expression in HGSC surgical specimens was associated with poor chemoresponse (p < 0.001) and primary resistance (p = 0.001). Expression in effusions and surgical specimens was unrelated to survival (p > 0.05). In conclusion, occludin expression is higher in HGSC compared to mesothelioma, and this protein is overexpressed in HGSC effusions, possibly reflecting changes in adhesion related to anchorage-independent growth in this microenvironment. Overexpression in post-chemotherapy compared to chemo-naïve effusions suggest a role in disease progression. Occludin expression in surgical specimens may be related to chemoresistance.

© 2023. The Author(s).

In plain English

This retrospective study from Oslo's Norwegian Radium Hospital measured occludin in two cancers. Occludin is a protein in the tight junctions that seal cells together. The cancers were tubo-ovarian high-grade serous carcinoma (HGSC) and mesothelioma. The authors stained 602 HGSC samples (417 fluid samples called effusions, plus 185 surgical specimens). For comparison they stained 87 pleural and peritoneal mesotheliomas (45 effusions, 42 surgical). The study did not examine asbestos exposure. Occludin was found in 587/602 (98%) HGSC samples and in 40/87 (46%) mesotheliomas. In mesotheliomas it was mostly limited to under 5% of cells. Reactive mesothelial cells were negative. In HGSC, occludin was higher in effusions than in surgical specimens, and higher in post-chemotherapy than chemo-naive effusions. In HGSC surgical specimens, occludin was associated with poor response to chemotherapy and with primary resistance. Occludin was not related to survival. The authors concluded that occludin may be a new diagnostic marker for HGSC, particularly in effusions, and may predict chemotherapy response, which they said needs validation in other series. They named limitations including the retrospective design and samples mostly not patient-matched.

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: Retrospective laboratory study of tumor samples stained by immunohistochemistry, with comparison to clinical and survival data
• Who was studied: 602 HGSC samples: 417 effusions from 417 patients, 1998 to 2017, and 185 surgical specimens from 114 patients, 1996 to 2007. For comparison, 87 pleural and peritoneal mesotheliomas (45 effusions, 42 surgical specimens; epithelioid or biphasic) submitted 1986 to 2008. All samples came from the Norwegian Radium Hospital, Oslo, Norway.
• Exposure: No asbestos or fiber exposure was studied. The factor measured was occludin protein staining in tumor cells, scored by the percentage of cells stained.
• Main results:
  • Occludin was found in 587/602 (98%) HGSC samples and in 40/87 (46%) mesotheliomas. In mesotheliomas it was mostly limited to under 5% of cells. Expression was significantly higher in HGSC (p less than 0.001).
  • Reactive mesothelial cells in the HGSC effusions did not stain for occludin.
  • In HGSC, occludin was higher in effusions than in surgical specimens (p less than 0.001).
  • In mesothelioma, expression did not differ between effusions and biopsies or surgical specimens (p = 0.902).
  • Occludin was higher in post-chemotherapy HGSC effusions (n = 136) than in chemo-naive effusions taken at diagnosis (n = 272) (p = 0.015).
  • In HGSC surgical specimens, occludin was associated with poor chemoresponse (p less than 0.001) and with primary resistance (p = 0.001).
  • In HGSC effusions, occludin was not related to overall survival in the whole cohort (p = 0.209).
  • In HGSC effusions, occludin was not related to progression-free survival in the whole cohort (p = 0.726).
  • In HGSC surgical specimens, occludin was not associated with overall survival (p = 0.648) or progression-free survival (p = 0.121).
• The authors' conclusion: The authors concluded that occludin is overexpressed in metastatic HGSC compared to mesothelioma and may be a new diagnostic marker of HGSC, particularly in effusions. They also concluded that it appears associated with disease progression and may predict chemotherapy response, though this should be validated in other series.
• Limitations the authors state:
  • Retrospective design
  • Most specimens were not matched by patient
  • No molecular data on HRD status, which may have affected chemotherapy response and outcome
  • Treatment dosage, drug combinations and extent of surgery varied over the study period
  • The study could not tell whether occludin differs between epithelioid and sarcomatoid mesothelioma, because nearly all cases were epithelioid
  • The mechanism by which occludin may confer chemoresistance still needs to be explored experimentally

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Carcinoma, Mesothelioma, Immunohistochemistry, Chemotherapy, Disease Progression.

Related studies

• Claudin-10 is a new candidate prognostic marker in metastatic high-grade serous carcinoma — B. Davidson, D. Doutel, et al. (2023)
• Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma — K. Brusegard, H.T. Stavnes, et al. (2012)
• Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma — E.T. Taube, C. Denkert, et al. (2017)
• Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks — X. Zhang, L. Chen, et al. (2018)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• CD24 is highly useful in differentiating high-grade serous carcinoma from benign and malignant mesothelial cells — B. Davidson (2016)

Browse return to medical research.