The association of P53 and Rb1 mutation in endometrial cancer development

Abstract Endometrial cancer (EC) is the most prevalent invasive malignancy in females and accounts for 6% of malignancies in women worldwide, with reported continued increasing incidence. Recently, many studies proved many mutations in EC and added four main types in the molecular classification of EC. FIGO classification of EC in 2023 was modified to change the staging according to P53 & POLE mutations. Since P53 & Rb1 are known cell cycle repressors, we generated our unique mouse model with P53 & Rb1 deletion (Pgr-cre/+, P53 Loxp/Loxp, Rb1 Loxp/Loxp) to study their role in the incidence and onset of EC development. Pgr-cre/+, P53 Loxp/Loxp, Rb1 Loxp/Loxp mice were generated by crossing Pgr-cre/+, P53 Loxp/Loxp male and Rb1 Loxp/Loxp female mice; the incidence, onset, and characteristics of EC were studied histologically and by IHC. We also studied the expression of P53 and Rb1 over a year in women diagnosed with EC after their informed consent to explore a concomitant expression. We found that Pgr-cre/+, P53 Loxp/Loxp, Rb1 Loxp/Loxp mice develop endometrial hyperplasia and cancer at a younger age with significant proliferation detected by Ki67 IHC and downregulation of P21 expression. While women had EC, we haven’t statistically significant results regarding the mean age of, no proven mutation, P53 mutation, and the associated P53&Rb1 mutation cases. We suggest that the double mutation of P53&Rb1 affects the age of incidence of EC in mice. At the same time, further multicenter studies, including higher sample sizes, are needed to prove or disprove this concept in women.