Open AccessLoss of B‐cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment
Author(s) -
Travaglino Antonio,
Raffone Antonio,
Saccone Gabriele,
Insabato Luigi,
Mollo Antonio,
De Placido Giuseppe,
Zullo Fulvio
Publication year - 2018
Publication title -
acta obstetricia et gynecologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.401
H-Index - 102
eISSN - 1600-0412
pISSN - 0001-6349
DOI - 10.1111/aogs.13452
Subject(s) - medicine , atypia , endometrial hyperplasia , hyperplasia , pathology , immunohistochemistry , endometrial cancer , differential diagnosis , endometrium , cancer
Endometrial hyperplasia is differentiated into benign or premalignant. Two histological classifications are used for this purpose: World Health Organization (WHO) classification, based on cytological atypia, disregarding glandular complexity, and endometrial intraepithelial neoplasia (EIN) classification, based on several different parameters. B‐cell lymphoma 2 (Bcl‐2) loss has been studied as immunohistochemical marker with the aim of improving the differential diagnosis between benign and premalignant hyperplasia. We aimed to evaluate: (A) Bcl‐2 loss as marker of endometrial precancer, by assessing it in proliferative endometrium, benign hyperplasia, premalignant hyperplasia, and endometrial cancer; (B) the diagnostic accuracy of Bcl‐2 in the differential diagnosis between benign and premalignant endometrial hyperplasia; (c) how the results change according to the histological classification and the thresholds of Bcl‐2 expression used. Material and methods Electronic databases were searched from their inception to March 2018. All studies assessing Bcl‐2 immunohistochemistry in endometrial specimens were included. Results In total, 20 observational studies assessing 1,278 specimens were included. Bcl‐2 loss rates were not significantly different between proliferative endometrium and benign hyperplasia ( P = 0.12) and between premalignant hyperplasia and endometrial cancer ( P = 0.53). Among hyperplasias, Bcl‐2 loss was significantly associated with premalignancy, according to both the WHO (OR = 4.39; P < 0.00001) and EIN classifications (OR = 6.07; P = 0.01), and also with architecture complexity (OR = 2.06; P = 0.02). Using the WHO classification, Bcl‐2 loss showed low diagnostic accuracy in detecting premalignant hyperplasia (area under the curve [AUC] = 0.708), with a sensitivity of 0.41, a specificity of 0.81, a positive likelihood ratio of 3.22, and a negative likelihood ratio of 0.69. Using the EIN classification, accuracy was high (AUC = 0.938), with a sensitivity of 0.18, a specificity of 0.97, a positive likelihood ratio of 5.16 and a negative likelihood ratio of 0.86. Thresholds of Bcl‐2 expression not involving a complete loss showed lower diagnostic accuracy with a slight increase in sensitivity, but a severe decrease in specificity. Conclusions B‐cell lymphoma 2 loss is a marker of endometrial precancer, with a high specificity and high diagnostic accuracy if the EIN classification is used. Thresholds of Bcl‐2 expression not involving a complete loss should not be considered. Bcl‐2 loss in endometrial hyperplasia may be a novel indication for treatment when precancerous features are ambiguous in a histological examination. Bcl‐2 loss correlates better with EIN classification than with the WHO classification, suggesting that glandular complexity is an important precancerous feature.