<scp>PAX</scp>2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta‐analysis of diagnostic accuracy

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: 62%

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

et al. 2019

APMIS

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“…For this reason, ARID1A does not appear adequate as a stand‐alone diagnostic marker of premalignant EH, but it may be useful as a ‘rule‐in’ test for diagnosis of precancer, due to its excellent specificity. In our previous studies, we found that Bcl‐2 and PAX2 were specific marker of premalignant EH , . On the other hand, PTEN, which is considered the key molecule in endometrial carcinogenesis, was too little specific to be clinically useful .…”

Section: Discussionmentioning

confidence: 97%

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

et al. 2019

APMIS

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Raffone A, Travaglino A, Saccone G, Cieri M, Mascolo M, Mollo A, Insabato L, Zullo F. Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS 2019; 127: 597-606.AT-rich interaction domain 1A (ARID1A) is a tumor suppressor protein involved in endometrioid carcinogenesis. The expression of ARID1A may be lost in the premalignant phase. Our aim was to assess ARID1A as: (i) diagnostic marker to differentiate premalignant endometrial hyperplasia (EH) form benign EH; (ii) prognostic marker for the risk of occult cancer in premalignant EH. A systematic review and meta-analysis were performed by searching electronic databases from their inception to October 2018 for all studies assessing ARID1A in EH by immunohistochemistry. Sensitivity, specificity, positive and negative likelihood ratios (LR+ and LRÀ), and diagnostic odds ratio (DOR) were calculated for both diagnostic and prognostic accuracy. LR+ > 5, LRÀ < 0.2, DOR > 25 defined good accuracy; LR+ > 10, LRÀ < 0.1, DOR > 100 defined excellent accuracy. Seven studies with 467 EH were included. As diagnostic marker, ARID1A showed sensitivity = 0.12, specificity = 0.99, LR+ = 4.34, LRÀ = 0.85, DOR = 5.12. As prognostic marker for occult cancer, ARID1A showed sensitivity = 0.33, specificity = 0.99, LR+ = 20.70, LRÀ = 0.49, DOR = 49.59. In conclusion, ARID1A loss is highly specific, but little accurate as diagnostic marker of premalignant EH. Instead, ARID1A loss in premalignant EH is an accurate and almost perfectly specific prognostic marker for coexistent cancer.

“…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.