p53abn high-risk endometrial cancer with PPP2R1A mutation might not benefit from adjuvant chemotherapy.

Abstract

Objectives: Recent studies have found that high-risk endometrial cancer frequently harbors mutations in tumor suppressor genes PPP2R1A and FBXW7. This study aimed to explore the prognostic utility of these genes and their potential to predict benefit from adjuvant treatment.

Methods: Tissue samples of 121 patients with high-risk endometrial cancer were collected. PPP2R1A, FBXW7, and POLE exonuclease domain mutations were detected using Sanger sequencing, while mismatch repair proteins and p53 expression were tested by immunohistochemistry.

Results: PPP2R1A and FBXW7 mutations were detected in 11.6% and 21.5% of tumors, respectively. PPP2R1A mutations occurred more frequently in nonendometrioid, high-grade, and advanced-stage tumors and were strongly correlated with poor prognosis. Importantly, PPP2R1A mutations were more frequent in the p53 abnormal (p53abn) subgroup than in the other 3 molecular subgroups (P = .011). In addition, patients with p53abn, PPP2R1A-mutated tumors showed poor prognosis regardless of whether they received adjuvant chemotherapy. In contrast, patients with p53abn, PPP2R1A wild-type tumors exhibited statistically significantly longer survival after adjuvant chemotherapy (P = .022). Similar associations were observed in the patients with p53abn, FBWX7 wild-type tumors.

Conclusions: PPP2R1A and FBXW7 status may be related to the current adjuvant chemotherapy outcome, particularly in endometrial cancer with the p53abn subtype. Thus, incorporating PPP2R1A and FBXW7 detection in the stratification and treatment decision-making process may be helpful.