High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma

Background: Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here we attempt to further portray the p53 pathway in USC by assessing p53 isoform expression. Methods: We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses of total p53 mRNA as well as quantitative distinction of p53 beta, p53 gamma, and the total mRNA of amino-terminal truncated Delta 40p53 and Delta 133p53 in a retrospective cohort of 37 patients with USC. TP53 mutation status was assessed by targeted massive parallel sequencing. Findings were correlated with clinical data. Results: The p53 isoform expression landscape in USCs was heterogeneous and dominated by total Delta 133p53, while the distinct p53 beta and p53 gamma variants were found at much lower levels. The isoform expression profiles varied between samples, while their expression was independent of TP53 mutation status. We found high relative p53 gamma expression to be associated with reduced progression-free survival (PFS). Conclusions: This is the first indication that elevated p53 gamma expression is associated with reduced PFS in USC. This singlecenter study may offer some insight in the landscape of p53 isoform expression in USC, but further validation studies are crucial to understand the context-dependent and tissue-specific role of the p53 isoform network in gynecological cancer.