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Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer.

Bodnar L, Stanczak A, Cierniak S, Smoter M, Cichowicz M, Kozlowski W, Szczylik C, Wieczorek M, Lamparska-Przybysz M - J Ovarian Res (2014)

Bottom Line: 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).These findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Military Institute of Medicine in Warsaw, 128 Szaserów Street, 04-141 Warsaw, Poland. lubo@esculap.pl.

ABSTRACT

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.

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Related in: MedlinePlus

Kaplan-Meier curves for PFS (A) and OS (B) by expression of membranous β-catenin. Red line: strong expression of β-catenin. Blue line: weak expression of β-catenin.
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Figure 2: Kaplan-Meier curves for PFS (A) and OS (B) by expression of membranous β-catenin. Red line: strong expression of β-catenin. Blue line: weak expression of β-catenin.

Mentions: To evaluate the impact of analysed proteins and histoclinical variables on EOC patients’ outcome, univariate analysis was performed. The analysis revealed the identification of several prognostic factors for PFS such as histopathologic cell type and membranous β-catenin expression. Age and residual tumour size revealed a prognostic trend for PFS (Table 2). Serous type of tumour was associated with shortened PFS (13.8 mo vs. 23.2 mo; p = 0.028). Younger age and greater residual tumour size showed a trend towards significance, while there was no association between PFS and performance status or tumour grade. Among analysed proteins, only membrane β-catenin was a prognostic factor in univariate analysis. Patients with tumours displaying strong expression of membranous β-catenin had shorter PFS than patients with a decreased level of the studied protein (9.9 mo vs. 22.8 mo; p = 0.024) (Figure 2). The expression of E-cadherin or WNT-1 were not associated with PFS. In the multivariate analysis, only intense expression of membrane β-catenin was an independent adverse prognostic factor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028).


Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer.

Bodnar L, Stanczak A, Cierniak S, Smoter M, Cichowicz M, Kozlowski W, Szczylik C, Wieczorek M, Lamparska-Przybysz M - J Ovarian Res (2014)

Kaplan-Meier curves for PFS (A) and OS (B) by expression of membranous β-catenin. Red line: strong expression of β-catenin. Blue line: weak expression of β-catenin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3926861&req=5

Figure 2: Kaplan-Meier curves for PFS (A) and OS (B) by expression of membranous β-catenin. Red line: strong expression of β-catenin. Blue line: weak expression of β-catenin.
Mentions: To evaluate the impact of analysed proteins and histoclinical variables on EOC patients’ outcome, univariate analysis was performed. The analysis revealed the identification of several prognostic factors for PFS such as histopathologic cell type and membranous β-catenin expression. Age and residual tumour size revealed a prognostic trend for PFS (Table 2). Serous type of tumour was associated with shortened PFS (13.8 mo vs. 23.2 mo; p = 0.028). Younger age and greater residual tumour size showed a trend towards significance, while there was no association between PFS and performance status or tumour grade. Among analysed proteins, only membrane β-catenin was a prognostic factor in univariate analysis. Patients with tumours displaying strong expression of membranous β-catenin had shorter PFS than patients with a decreased level of the studied protein (9.9 mo vs. 22.8 mo; p = 0.024) (Figure 2). The expression of E-cadherin or WNT-1 were not associated with PFS. In the multivariate analysis, only intense expression of membrane β-catenin was an independent adverse prognostic factor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028).

Bottom Line: 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).These findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Military Institute of Medicine in Warsaw, 128 Szaserów Street, 04-141 Warsaw, Poland. lubo@esculap.pl.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus