Claudin-10 is a new candidate prognostic marker in metastatic high-grade serous carcinoma

Our plain-English summary of Claudin-10 is a new candidate prognostic marker in metastatic high-grade serous carcinoma, by B. Davidson, D. Doutel, A. Holth, et al (Virchows Archiv, 2023).

The study

• Authors: B. Davidson, D. Doutel, A. Holth, D.A. Nymoen
• Journal: Virchows Archiv
• Published: 2023;482(6):975-982
• Cited by: 8 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 claudin-10 in high-grade serous carcinoma (HGSC). Claudin-10 protein expression by immunohistochemistry was analyzed in 588 HGSC (414 effusions, 174 surgical specimens). Expression in mesotheliomas (n = 97; 47 effusions, 50 surgical specimens) was studied for comparative purposes. CLDN10 mRNA expression by quantitative RT-PCR (qRT-PCR) was analyzed in 40 HGSC effusions. Claudin-10 protein expression was found in 360/588 (61%) HGSC vs. 19/97 (20%) mesotheliomas (p < 0.001), and was higher in HGSC surgical specimens compared to effusions (p < 0.001). qRT-PCR confirmed the presence of CLDN10 mRNA in HGSC effusions. High (> 25%) claudin-10 expression in HGSC effusions was significantly associated with shorter overall survival (OS; p = 0.036) and progression-free survival (PFS; p = 0.045) in univariate analysis, and was an independent prognosticator of OS in multivariate analysis (p = 0.045). In conclusion, claudin-10 protein expression is higher in HGSC compared to mesothelioma, although the diagnostic power of this marker appear to be lesser than other claudin family members. Claudin-10 expression in HGSC effusions is marker of more aggressive disease.

© 2023. The Author(s).

In plain English

This Oslo laboratory study measured claudin-10 protein in 588 high-grade serous carcinoma (HGSC) specimens. For comparison, it tested 97 pleural and peritoneal mesotheliomas. The article did not examine asbestos exposure. Claudin-10 staining was found in 360 of 588 HGSC (61%) and 19 of 97 mesotheliomas (20%), a statistically significant difference. Among HGSC, staining was more common in surgical specimens (146 of 174) than in fluid (effusion) specimens (214 of 414). In patients with HGSC effusions, high claudin-10 staining (more than 25% of tumor cells) was linked to shorter overall survival (409 patients; mean 32 versus 42 months) and shorter progression-free survival (394 patients; mean 9 versus 13 months). After other factors were taken into account, it remained an independent predictor of overall survival but not of progression-free survival. Higher CLDN10 mRNA in 40 effusion patients, and higher claudin-10 protein in 71 surgical-specimen patients, went with shorter overall survival, but not significantly. The authors concluded that claudin-10 is higher in HGSC than in mesothelioma but a weaker diagnostic marker than other claudins, and that it marks more aggressive disease in HGSC effusions.

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 pathology study of archived tumor specimens, using immunohistochemistry for claudin-10 protein, qRT-PCR for CLDN10 mRNA in a subset, and survival analysis in HGSC patients
• Who was studied: The study included 588 HGSC specimens: 414 effusions from 414 patients collected 1998 to 2017, and 174 surgical specimens from 109 patients resected 1996 to 2007. For comparison it included 97 pleural and peritoneal mesotheliomas (47 effusions, 50 surgical specimens) from patients with epithelioid or biphasic mesothelioma, submitted 1986 to 2008. All specimens came from the Norwegian Radium Hospital, Oslo.
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was claudin-10 protein in tumor cells, scored by the percentage of stained cells, with high defined as more than 25%. CLDN10 mRNA levels were also measured.
• Main results:
  • Claudin-10 protein was found in 360/588 (61%) HGSC specimens vs. 19/97 (20%) mesotheliomas. Expression was significantly higher in HGSC (p less than 0.001).
  • High expression (more than 25% of cells) was seen in 80/414 (19%) HGSC effusions, 43/174 (25%) HGSC surgical specimens, 2/47 (4%) mesothelioma effusions and 1/50 (2%) mesothelioma biopsies/resections.
  • In HGSC, staining of any extent was found in 146/174 (84%) surgical specimens vs. 214/414 (52%) effusions (p less than 0.001).
  • No such difference was seen between mesothelioma effusions and solid specimens (p = 0.424).
  • Survival data were available for 409 of the 414 patients with HGSC effusions.
  • In HGSC effusion patients, high claudin-10 expression was associated with significantly shorter overall survival (p = 0.036) and progression-free survival (p = 0.045) in univariate analysis.
  • In the overall-survival analysis of 409 HGSC effusion patients, those with high claudin-10 expression (n = 79) had a mean overall survival of 32 months. Those with low expression (n = 330) had a mean of 42 months.
  • Progression-free survival was analysed in 394 HGSC effusion patients with PFS data. Those with high claudin-10 expression (n = 77) had a mean progression-free survival of 9 months, compared with 13 months for those with low expression (n = 317).
  • In multivariate analysis of overall survival, claudin-10 expression (p = 0.045), FIGO stage and residual disease volume were independent prognosticators. Age was not (p = 0.513).
  • In multivariate analysis of progression-free survival, claudin-10 was not an independent prognosticator (p = 0.118). Only residual disease volume was.
  • In the 40-patient qRT-PCR group (HGSC effusions), higher CLDN10 mRNA levels were associated with shorter overall survival, but not significantly (mean 29 vs. 38 months; p = 0.214).
  • In the 71 patients with survival data in the surgical-specimen cohort, whose specimens were assessed by claudin-10 protein staining, higher claudin-10 was likewise associated with shorter overall survival, but not significantly (mean 43 vs. 53 months; p = 0.282).
  • In HGSC effusions, claudin-10 protein expression was significantly higher in specimens from younger patients (p = 0.013).
• The authors' conclusion: The authors concluded that claudin-10 is overexpressed in HGSC compared to mesothelioma, but with lesser sensitivity and specificity as a diagnostic marker than other claudin family members. They also concluded that claudin-10 expression in HGSC effusions is a marker of more aggressive disease.
• Limitations the authors state:
  • Most surgical specimens were not from the same patients as the effusions.
  • Because the SEE-FIM procedure was not used during the collection period, surgical specimens could not be classified as primary or metastatic.
  • Only 104 specimens could be compared with the earlier study of claudins 1, 3, 4 and 7.
  • The authors' proposed explanation for the link between claudins and poor outcome (chemoresistance and/or genomic signatures) needs further research to validate.

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, Immunohistochemistry, Mesothelioma, Overall Survival, Progression-Free Survival, Multivariate Analysis.

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