Open AccessPAX 2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta‐analysis of diagnostic accuracy
Author(s) -
Raffone Antonio,
Travaglino Antonio,
Saccone Gabriele,
Mascolo Massimo,
Insabato Luigi,
Mollo Antonio,
De Placido Giuseppe,
Zullo Fulvio
Publication year - 2019
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.13512
Subject(s) - medicine , endometrial cancer , diagnostic odds ratio , immunohistochemistry , receiver operating characteristic , endometrial hyperplasia , gynecology , univariate analysis , pathology , carcinogenesis , endometrium , immunostaining , differential diagnosis , hyperplasia , oncology , cancer , multivariate analysis
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 2017 European Society of Gynaecological Oncology guidelines recommend paired box 2 protein ( PAX 2) immunohistochemistry to identify precancerous EH . However, methods for interpreting immunostaining and diagnostic accuracy are not defined, and the role of PAX 2 in endometrial carcinogenesis is unclear. We aimed to assess: (a) PAX 2 expression throughout endometrial carcinogenesis, from normal endometrium to benign EH , precancerous EH , and endometrial cancer (EC); (b) the diagnostic accuracy of PAX 2 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 PAX 2 immunohistochemistry in normal endometrium, EH , and EC were included. Univariate comparisons of PAX 2 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 PAX 2 expression were significantly more common in EC and precancerous EH than benign EH . Diagnostic accuracy was moderate for both PAX 2 complete loss and decrease (areas under the curve 0.829 and 0.876, respectively). PAX 2 complete loss with EIN system showed the best results (sensitivity = 0.72; specificity = 0.95; DOR = 43.13). Conclusions PAX 2 seems to behave as a tumor suppressor in endometrial carcinogenesis. PAX 2 is an accurate marker of precancerous EH ; complete loss of PAX 2 and EIN classification appear as the optimal diagnostic criteria.