Claudin-4 Expression is Associated With Survival in Ovarian Cancer But Not With Chemotherapy Response

Autor: Linda Werner Hartman, Ingrid Hedenfalk, Jenny-Maria Jönsson, Susanne Malander, Mef Nilbert, Anna Måsbäck, Laura Martin de la Fuente, Anna Ebbesson
Rok vydání: 2017
Předmět:
0301 basic medicine
Pathology
endocrine system diseases
Kaplan-Meier Estimate
Carcinoma
Ovarian Epithelial
Cohort Studies
0302 clinical medicine
Ovarian carcinoma
Medicine
Neoplasms
Glandular and Epithelial
Claudin-4
Aged
80 and over
Ovarian Neoplasms
Prognostic factor
Tissue microarray
BRCA1 Protein
Hazard ratio
Obstetrics and Gynecology
Middle Aged
030224 pathology
Prognosis
Immunohistochemistry
female genital diseases and pregnancy complications
Pathology of the Upper Genital Tract: Original Article
030220 oncology & carcinogenesis
Cohort
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Platinum resistance
Female
Chemotherapy response
Adult
medicine.medical_specialty
Disease-Free Survival
Pathology and Forensic Medicine
03 medical and health sciences
Carcinoma
Biomarkers
Tumor
Humans
Claudin
Aged
Platinum
BRCA2 Protein
Sweden
business.industry
medicine.disease
Log-rank test
030104 developmental biology
Drug Resistance
Neoplasm
Tissue Array Analysis
Relative risk
Cancer research
business
Ovarian cancer
Zdroj: International Journal of Gynecological Pathology
ISSN: 1538-7151
Popis: Supplemental Digital Content is available in the text.
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 χ2 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
Databáze: OpenAIRE
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