Expression of PAX2 and PTEN in Oestrogen-Driven Endometrial Hyperplasia and Neoplasia

Abstract

Endometrial hyperplasia is of paramount clinical implication as it is usually seen to precede endometrioid adenocarcinoma. However, clinicians and pathologists have always been uncertain about the distinction between innocuous hyperplasia from their sinister counterparts. This has serious implications, for the latter lesion has a greater propensity for progressing into adenocarcinoma and needs deft clinical intervention in the form of adequate progestational exposure or surgery. Thirty cases diagnosed as endometrial hyperplasia on endometrial biopsies were retrieved from the archives and reclassified as per the EIN criteria. Thirty cases each of proliferative endometrium and endometrioid carcinoma were also included. Immunohistochemistry with antibodies against PAX2 and PTEN was performed, and the extent of loss of expression was scored. A total of ten cases of EIN were identified, all of whom were initially diagnosed as complex hyperplasia with atypia. All cases of proliferative endometrium showed retained expression of PAX2 and PTEN. In contrast, all cases of endometrioid carcinoma showed complete loss of PAX2 and PTEN. The EIN cases showed partial loss of both PAX2 and PTEN expression. Loss of PAX2 expression in EIN showed a specificity and positive predictive value of 90% and 83.33%, respectively. The advent of the EIN criteria has made identification of clinically significant endometrial precancerous lesion more acceptable and reproducible. However, in cases of ambiguity, the use of antibodies against certain protein molecules which reflect the genes involved in the stepwise carcinogenesis would be of great utility in the hands of the pathologist. In comparison with PTEN, the use of PAX2, which gives a crisp nuclear positivity and has a lower percentage of loss of expression in normal endometrium, can be used as part of the algorithm in accurately identifying the precancerous endometrium.