Loss of PTEN expression as diagnostic marker of endometrial precancer: a systematic review and meta-analysis

Introduction: Endometrial hyperplasia may be either a benign proliferation or a premalignant lesion. In order to differentiate these two conditions, two possible histologic classifications can be used: the World Health Organization (WHO) classification and the endometrial intraepithelial neoplasia (EIN) classification. The 2017 European Society of Gynaecological Oncology guidelines recommend the use of immunohistochemistry for tumor suppressor protein phosphatase and tensin homolog (PTEN) to improve the differential diagnosis. Nonetheless, its diagnostic accuracy has never been defined. We aimed to assess the diagnostic accuracy of immunohistochemistry for PTEN in the differential diagnosis between benign and premalignant endometrial hyperplasia. Material and methods: Electronic databases were searched from their inception to May 2018 for studies assessing immunohistochemical expression of PTEN in endometrial hyperplasia specimens. PTEN status (“loss” or “presence”) was the index test; histological diagnosis (“precancer” or “benign”) was the reference standard. Sensitivity, specificity, positive and negative likelihood ratios (LR+, LR−), diagnostic odds ratio (DOR), and area under the curve (AUC) on summary receiver operating characteristic curves were calculated (95% CI), with a subgroup analysis based on the histologic classification adopted (WHO vs EIN). Results: Twenty-seven observational studies with 1736 cases of endometrial hyperplasia were included. Pooled estimates showed low diagnostic accuracy: sensitivity 54% (95% CI 50%-59%), specificity 66% (63%-69%), LR+ 1.55 (1.29-1.87), LR− 0.72 (0.62-0.83), DOR 3.56 (2.02-6.28), AUC 0.657. When the WHO subgroup was compared with the EIN subgroup, higher accuracy (AUC 0.694 vs. 0.621), and higher heterogeneity in all analyses, were observed. Conclusions: Immunohistochemistry for PTEN showed low diagnostic usefulness in the differential diagnosis between benign and premalignant endometrial hyperplasia. In the absence of further evidence, the recommendation about its use should be reconsidered.