Dusp6 immunohistochemistry is associated with the response of atypical endometrial hyperplasia and early endometrial cancer to conservative treatment

Abstract

Objective: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC.Methods: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve.Results: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53). Conclusion:Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy.

Fertility-Sparing Approach in Patients with Endometrioid Endometrial Cancer Grade 2 Stage IA (FIGO): A Qualitative Systematic Review

“…In fact, the lack of expression of Dusp6 was an important sign of potential therapy failure, associated with poor response. BioMed Research International In a more recent study, Travaglino et al [70] analyzed in detail the role of Dusp6 as predictive marker of response of AEH and EEC in women undergoing to conservative treatment, highlighting that a weak expression of Dusp6, with moderate predictive accuracy, represents an important predictor of resistance of fertility-sparing treatment in AEH/ EECs. Although both studies have obtained encouraging results about Dust6, as an important marker of response to progestin treatment, they have not been included in this review as Zhang et al deals with only endometrial hyperplasia, while Travaglino et al study is consecutive to the data sources, conducted from 2010 to September 2021.…”