Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study)

Simple Summary There is a lack of literature on the role of molecular classification in patients with morphological low-risk EC. We aimed to evaluate the incidence and prognostic role of p53 mutations in this specific subgroup of patients. Our findings show that 4.9% of low-risk EC are p53abn; the OR for the recurrence of p53abn versus p53wt patients was 5.23-CI 95% 0.98-27.95, p = 0.053. No difference in OS was observed between the two groups. Recurrences were mostly local and occur two years after diagnosis. Our data might serve as a valuable tool for clinicians' everyday practice, but larger prospective studies are urgently needed.Abstract No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.