Nuclear expression of β-catenin in endometrial hyperplasia as marker of premalignancy

We aimed to assess (1)-whether nuclear β-catenin is a marker of endometrial precancer, and (2)-the diagnostic accuracy of β-catenin immunohistochemistry in the differential diagnosis between benign and premalignant endometrial hyperplasia (EH), defining criteria for its use. Electronic databases were searched for studies evaluating β-catenin immunohistochemistry in normal endometrium (NE), benign and/or premalignant EH, and endometrioid carcinoma (EC). Odds ratio (OR; p < 0.05), sensitivity, specificity, diagnostic OR (DOR), positive and negative likelihood ratios (LR+, LR-) were calculated. Subgroup analyses were based on the classification system used (WHO or EIN) and criteria to define aberrant β-catenin expression (only nuclear or cytoplasmic/nuclear). Twelve studies with 1510 specimens were included. Nuclear β-catenin rate significantly increased from NE to benign EH (OR = 26.01; p = 0.0002, only in WHO subgroup), and from benign EH to premalignant EH (OR = 3.89; p = 0.0002; more markedly in EIN subgroup), but not from premalignant EH to EC (OR = 0.78; p = 0.29). Nuclear β-catenin accuracy was very low in WHO subgroup (sensitivity = 0.40, specificity = 0.76, LR+ = 1.85, LR- = 0.72; DOR = 2.89) and moderate in EIN subgroup (sensitivity = 0.19, specificity = 1.00, LR+ = 14.80, LR- = 0.83; DOR = 18.14). Cytoplasmic/nuclear β-catenin accuracy was absent in WHO subgroup (sensitivity = 0.45, specificity = 0.54, LR+ = 1.01, LR- = 1.01; DOR = 0.99) and low in EIN subgroup (sensitivity = 0.57, specificity = 0.86, LR+ = 3.63, LR- = 0.51; DOR = 8.30). Considering nuclear expression and using EIN system, β-catenin immunohistochemistry might be reliable as rule-in test for diagnosis of endometrial precancer, with perfect specificity and moderate overall accuracy.