Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria

et al. 2019

APMIS

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The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non‐atypical EH. A systematic review and meta‐analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non‐atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p‐value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non‐atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non‐atypical EH. Complex non‐atypical EH may be regarded as a low‐risk premalignant lesion rather than a benign condition.

Section: Discussionmentioning

confidence: 86%

Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia

et al. 2019

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“…Data were also subdivided into subgroups based on: administration route of progestins (oral or intrauterine), due to the recognized superiority of levonorgestrel‐medicated intrauterine device (LNG‐IUD); histological diagnosis (atypical EH/EEC or non‐atypical EH), since the first two are neoplastic lesions and the latter one is a reactive condition …”

Section: Methodsmentioning

confidence: 99%

“…• histological diagnosis (atypical EH/EEC or non-atypical EH), since the first two are neoplastic lesions and the latter one is a reactive condition. [31][32][33][34] The predictive value of ER and PR was assessed as relative risk (RR)…”

Section: Ta B L E 1 Characteristics Of the Included Studiesmentioning

confidence: 99%

Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta‐analysis

Acta Obstet Gynecol Scand

et al. 2019

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Introduction Progestins are used as conservative treatment of endometrial hyperplasia (EH) and early endometrial cancer (EEC). We aimed to assess whether immunohistochemical expression of estrogens and progesterone receptors (ER and PR) predicts the treatment response. Material and methods Electronic databases were searched for studies assessing ER and PR expression in EH and EEC treated with progestins. Relative risk for poor response, sensitivity, specificity, diagnostic odds ratio positive and negative likelihood ratios (LR+ and LR−) and area under the curve (AUC) on summary receiver operating characteristic curve were calculated. Subgroup analyses were based on administration route (oral progestin or levonorgestrel‐intrauterine device) and on histological diagnosis (atypical EH/EEC or non‐atypical EH). Only high accuracy (AUC > 0.9; LR+ >10; LR− <0.1) was considered determining for the clinical practice. Results Thirteen studies with 635 patients were included in the systematic review. Studies at high risk of bias were excluded from the meta‐analysis. Negative ER expression did not significantly predict poor response (P = 0.16), with low predictive accuracy (AUC = 0.637). Negative PR significantly predicted poor response (P = 0.01), with moderate accuracy (AUC = .806). In the oral progestin subgroup, neither ER (P = 0.55) nor PR (P = 0.18) had significant predictive value. In the levonorgestrel‐intrauterine device subgroup, both ER (P < 0.0001) and PR (P = 0.02) were significantly predictive of good response, although the accuracy was suboptimal (LR+ 6.02 and 2.48, respectively; LR− 0.59 and 0.55, respectively). The atypical EH/EEC subgroup showed non‐significant results. Data about non‐atypical EH were not extractable. Conclusions ER and PR expressions are significantly predictive of response in EH and EEC treated with a levonorgestrel‐intrauterine device but not with oral progestins. However, their accuracy is insufficient to be determining in the clinical practice.

“…4 The EIN system categorizes EH into "benign EH" and "endometrial intraepithelial neoplasia," based on a combination of histomorphologic criteria. 7 To date, histologic examination is the reference standard in differential diagnosis between benign and premalignant EH. 5 On the other hand, the revised 2014 WHO classification has used "atypical EH" and "endometrial intraepithelial neoplasia" as synonyms.…”

Section: Introductionmentioning

confidence: 99%

“…This novel classification categorized EH into three categories: benign EH, EIN without cytologic atypia (at lower risk), and EIN with cytologic atypia (at higher risk). 7 To date, histologic examination is the reference standard in differential diagnosis between benign and premalignant EH. Nonetheless, this method is characterized by poor inter-and intra-observer reproducibility.…”

Section: Introductionmentioning

confidence: 99%

PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta‐analysis of diagnostic accuracy

Acta Obstet Gynecol Scand

et al. 2019

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Abbreviations: AUC, area under the curve; DOR, diagnostic odds ratio; EC, endometrial cancer; EH, endometrial hyperplasia; EIN, endometrial intraepithelial neoplasia; ESGO, European Society of Gynaecological Oncology; LR+, positive likelihood ratio; LR−, negative likelihood ratio; NE, normal endometrium; PAX2, paired box 2 protein; SROC, summary receiver operating characteristic; WHO, World Health Organization. Abstract Introduction: Benign and precancerous endometrial hyperplasias (EH) are differentiated according to two alternative histomorphologic classifications: World Health Organization (WHO) or endometrial intraepithelial neoplasia (EIN) system. The 2017European Society of Gynaecological Oncology guidelines recommend paired box 2 protein (PAX2) immunohistochemistry to identify precancerous EH. However, methods for interpreting immunostaining and diagnostic accuracy are not defined, and the role of PAX2 in endometrial carcinogenesis is unclear. We aimed to assess: (a) PAX2 expression throughout endometrial carcinogenesis, from normal endometrium to benign EH, precancerous EH, and endometrial cancer (EC); (b) the diagnostic accuracy of PAX2 immunohistochemistry in diagnosing precancerous EH, defining criteria for its use. Material and methods:Electronic databases were searched for from their inception to July 2018. All studies evaluating PAX2 immunohistochemistry in normal endometrium, EH, and EC were included. Univariate comparisons of PAX2 expression were performed with Fisher's exact test (significant P < .05). Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve on summary receiver operating characteristic curves were calculated. Subgroup analyses were based on expression thresholds (decrease vs complete loss) and classifications used (WHO vs EIN). Results:Six studies with 266 normal endometrium, 586 EH, and 114 EC were included. Both decrease and complete loss of PAX2 expression were significantly more common in EC and precancerous EH than benign EH. Diagnostic accuracy was moderate for both PAX2 complete loss and decrease (areas under the curve 0.829 and 0.876, respectively). PAX2 complete loss with EIN system showed the best results (sensitivity = 0.72; specificity = 0.95; DOR = 43.13).Conclusions: PAX2 seems to behave as a tumor suppressor in endometrial carcinogenesis. PAX2 is an accurate marker of precancerous EH; complete loss of PAX2 and EIN classification appear as the optimal diagnostic criteria. K E Y W O R D Sbiomarker, cancer precursor, endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrioid adenocarcinoma, paired box 2 protein Key message PAX2 loss is an accurate diagnostic marker of endometrial precancer. A complete loss of PAX2 and the EIN classification appear as the optimal diagnostic criteria.