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Claudin-4 expression is associated with progression free survival in ovarian cancer, but not with chemotherapy response

Martin de la Fuente, L. LU ; Malander, S. LU orcid ; Hartman, L. LU orcid ; Jönsson, J.-M. LU ; Ebbesson, A. LU ; Nilbert, M. LU ; Måsbäck, A. LU and Hedenfalk, I. LU orcid (2017) In International Journal of Gynecological Pathology 37(2). p.101-109
Abstract
The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2... (More)
The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Gynecological Pathology
volume
37
issue
2
pages
101 - 109
publisher
Lippincott Williams & Wilkins
ISSN
0277-1691
project
Ovarian carcinoma, early detection and prognostication
language
English
LU publication?
yes
id
4540fefa-a351-4ab8-b918-1b1e86f1ec33
alternative location
https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5815640&blobtype=pdf
date added to LUP
2017-11-09 14:35:50
date last changed
2022-09-15 12:36:40
@article{4540fefa-a351-4ab8-b918-1b1e86f1ec33,
  abstract     = {{The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of &gt;1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P&lt;0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.}},
  author       = {{Martin de la Fuente, L. and Malander, S. and Hartman, L. and Jönsson, J.-M. and Ebbesson, A. and Nilbert, M. and Måsbäck, A. and Hedenfalk, I.}},
  issn         = {{0277-1691}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{101--109}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{International Journal of Gynecological Pathology}},
  title        = {{Claudin-4 expression is associated with progression free survival in ovarian cancer, but not with chemotherapy response}},
  url          = {{https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5815640&blobtype=pdf}},
  volume       = {{37}},
  year         = {{2017}},
}