Introduction/Background The growing adoption of molecular and genomic characterization is changing the current landscape of treatment of endometrial cancer patients. Using the surrogate molecular classification endometrial cancer patients are classified into four subgroups: POLE mutated, MMRd/MSI-H, p53 abnormal, and no specific mutational profile (NSMP). However, there are few patients (called multiple classifiers) harboring two or more mutational patterns. Since the rarity of this occurrence, evidence regarding multiple classifiers is still limited. Here, we described the characteristics and outcomes of multiple classifiers.

Methodology This is a multi-institutional retrospective study. Apparent early-stage endometrial cancer patients were evaluated via conventional pathological analysis and via immunohistochemistry and next-generation sequencing.

Results Charts of 72 multiple classifiers were reviewed. Median (range) follow-up was 9.8 (1.2, 37.5) months. Overall, 31 (43%) patients had a POLE mutation. Patients with POLE plus MMRd/MSI-H, POLE plus p53, and POLE plus MMRd/MSI-H, and p53 were 6 (8.3%), 20 (27.8%), and 5 (6.9%), respectively. Among those 31 patients, six had postoperative adjuvant therapies, and no recurrence occurred (median follow-up: 10.5 months (seven patients had at least 2-year follow-up)). Forty-one (56.9%) patients were diagnosed with tumors harboring both p53 plus MMRd/MSI-H. Adjuvant therapy was administered in 25/41 patients (60.9%). Four (9.8%) recurrences occurred after a median follow-up of 8.9 months (eleven non-recurring patients had at least a 2-year follow-up).

Conclusion Multiple-classifier endometrial cancers are characterized by a good prognosis. POLE mutation seems to confer protection in multiple classifier endometrial cancer even in the case of the presence of MMRd/MSI-H and/or p53 abnormality. Prospective studies with long-term follow-up are needed.

Disclosures None.