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Nuclear β‐catenin and CDX 2 expression in ovarian endometrioid carcinoma identify patients with favourable outcome
Author(s) -
Wang Linyuan,
Rambau Peter F,
Kelemen Linda E,
Anglesio Michael S,
Leung Samuel,
Talhouk Aline,
Köbel Martin
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13772
Subject(s) - medicine , catenin , cancer research , oncology , biology , gene , wnt signaling pathway , genetics
Aims Ovarian endometrioid carcinoma ( EC ) generally has a good prognosis. Adjuvant chemotherapy can be spared in low‐stage disease, but prognostic biomarkers are needed to refine the treatment threshold. Wnt/β‐catenin signalling is commonly altered in EC . We examined immunohistochemical expression of nuclear β‐catenin and CDX 2 as prognostic biomarkers for EC ; both are mediators of the Wnt pathway. Methods and results We evaluated two ovarian EC cohorts, discovery set ( n = 183) and validation set ( n = 174), with ovarian cancer‐specific survival ( OCSS ) as the primary end‐point. In univariable analysis, nuclear β‐catenin expression was significantly associated with longer OCSS in the discovery set [hazard ratio ( HR ) = 0.36, 95% confidence interval ( CI ) = 0.16–0.74, P = 0.004] and the validation set ( HR = 0.35, 95% CI = 0.11–0.89, P = 0.006). Similar significant associations were observed with CDX 2 expression in the discovery set ( HR = 0.25, 95% CI = 0.11–0.50, P < 0.001) and validation set ( HR = 0.27, 95% CI = 0.07–0.75, P = 0.020). In multivariable analysis, combined positivity of both markers was significantly associated with longer OCSS in the discovery set ( HR = 0.20, 95% CI = 0.06–0.49, P < 0.001) and in the validation set ( HR = 0.33 95% CI = 0.07–0.1.06, P = 0.047). In a stratified analysis for stage IC / II EC , combined positivity identified a subset of patients with a significantly longer OCSS in the discovery cohort but only a non‐significant trend in the validation cohort. Conclusions Nuclear β‐catenin and CDX 2 expression individually or in combination are validated prognostic markers for ovarian EC . However, their full potential to stratify low risk patients at adjuvant threshold awaits further multimarker study.