Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer.
BACKGROUND
β-catenin is the key protein in the WNT signalling pathway and it forms adherent junctions together with E-cadherin. In ovarian carcinoma, abnormal expression of β-catenin, E-cadherin and WNT-1 was observed, but their prognostic and predictive role is unclear. The aim of this study was to clarify the prognostic and predictive role of E-cadherin, β-catenin and WNT-1 in advanced epithelial ovarian carcinoma (AEOC).


METHODS
The expression of E-cadherin, β-catenin and WNT-1 was determined by immunohistochemistry in AEOC. The correlation between expression of these proteins and progression-free survival (PFS) and overall survival (OS) was evaluated. Statistical analyses included Kaplan-Meier estimation, log-rank test, Spearman correlation and Cox proportional-hazards model.


RESULTS
In ovarian cancer, intense expression of E-cadherin, β-catenin and WNT-1 was found. In multivariate analysis, strong membrane β-catenin expression was an independent unfavourable predictor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028), while in univariate analysis, strong membrane β-catenin expression was a prognostic factor for OS in patients with AOC (p = 0.039). In multivariate analysis, only resistance to first-line chemotherapy was an adverse independent prognostic factor for OS (HR 16.84; 95% CI 5.07-55.98; p < 0.0001). Additionally, strong membranous β-catenin expression was associated with resistance to platinum-based chemotherapy (p = 0.027).


CONCLUSIONS
These findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.
Department of Oncology, Military Institute of Medicine in Warsaw, 128 Szaserów Street, 04-141 Warsaw, Poland. lubo@esculap.pl.
Lubomir
L
Bodnar
Aleksandra
A
Stanczak
Szczepan
S
Cierniak
Marta
M
Smoter
Marzena
M
Cichowicz
Wojciech
W
Kozlowski
Cezary
C
Szczylik
Maciej
M
Wieczorek
Monika
M
Lamparska-Przybysz
D000368:Aged; D015703:Antigens, CD; D001706:Biopsy; D015820:Cadherins / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000032:analysis*; D051176:beta Catenin / Q000032:analysis*
D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin