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Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response

Martín De La Fuente, Laura LU ; Malander, Susanne LU ; Hartman, Linda LU ; Jönsson, Jenny Maria LU ; Ebbesson, Anna LU ; Nilbert, Mef LU ; Måsbäck, Anna LU and Hedenfalk, Ingrid LU (2018) 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... (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.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Claudin-4, Ovarian carcinoma, Platinum resistance, Prognostic factor
in
International Journal of Gynecological Pathology
volume
37
issue
2
pages
101 - 109
publisher
Lippincott Williams and Wilkins
external identifiers
  • scopus:85043515230
ISSN
0277-1691
DOI
10.1097/PGP.0000000000000394
language
English
LU publication?
yes
id
7f063ba3-ff36-4f3c-80f9-3c1e5fcb56be
date added to LUP
2018-03-26 16:19:37
date last changed
2019-04-23 04:29:49
@article{7f063ba3-ff36-4f3c-80f9-3c1e5fcb56be,
  abstract     = {<p>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.</p>},
  author       = {Martín De La Fuente, Laura and Malander, Susanne and Hartman, Linda and Jönsson, Jenny Maria and Ebbesson, Anna and Nilbert, Mef and Måsbäck, Anna and Hedenfalk, Ingrid},
  issn         = {0277-1691},
  keyword      = {Claudin-4,Ovarian carcinoma,Platinum resistance,Prognostic factor},
  language     = {eng},
  number       = {2},
  pages        = {101--109},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {International Journal of Gynecological Pathology},
  title        = {Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response},
  url          = {http://dx.doi.org/10.1097/PGP.0000000000000394},
  volume       = {37},
  year         = {2018},
}