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

Abstract

We aimedto 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 tobenign EH (OR=26.01; p=0.0002, only in WHO subgroup), and from benign EH topremalignant 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.