Immunohistochemical Nuclear Expression of β-Catenin as a Surrogate of CTNNB1 Exon 3 Mutation in Endometrial Cancer

Objectives: CTNNB1 exon 3 mutations have shown independent prognostic value in endometrial cancer. We aimed to assess whether nuclear β-catenin expression is an accurate surrogate, as immunohistochemistry is cheaper, faster, and more widely applicable than sequencing.

Methods: A systematic review was performed by searching electronic databases for all studies assessing the association between β-catenin immunohistochemical expression and CTNNB1 mutations. Meta-analysis of diagnostic accuracy was performed by calculating sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) on summary receiver operating characteristic curves.

Results: Fifteen observational studies with 1,158 endometrial carcinomas were included. Pooled estimates showed sensitivity = 0.88, specificity = 0.85, LR+ = 4.57, LR- = 0.20, DOR = 27.16, and high diagnostic accuracy (AUC = 0.91).

Conclusions: Nuclear expression of β-catenin is an accurate immunohistochemical surrogate of CTNNB1 exon 3 mutations and thus might be considered in the risk stratification of endometrial cancer.