The Impact of Molecular Profile Changes and Other Histopathological Parameters on Endometrial Cancer Recurrence.

Background/Objectives: Numerous innovations have changed diagnosis and treatment of endometrial cancer in recent years, with molecular classification being a major factor. Limited data exist on how molecular classification changes in recurrence or metastasis and what effect this may have on therapy. This retrospective study aimed to compare the molecular classification and other histopathological parameters of the primary tumor with those of recurrence or metastasis and to discuss their implications. Methods: A total of 43 patients with primary endometrial cancer and histologically confirmed recurrence treated at the Tuebingen University Women's Hospital between January 2003 and January 2017 were identified within a cohort of 964 cases. Immunohistochemistry for mismatch-repair status, estrogen receptor, p53 and L1CAM, as well as next-generation sequencing of the POLE genes were performed. Further histopathological and clinical data were collected and statistical analyses were performed. Results: No POLE-mutated patients were found. A higher proportion of high-grade tumors was observed in the recurrence (30% vs. 46%). All p53-mutated patients remained p53-mutated, while a changed molecular profile of the NSMP and MMRd subtypes was observed in nine patients (21%). L1CAM remained stable in 70% of the patients. A change in molecular profile was not associated with altered prognosis. Conclusions: Our study underlines the importance of additional histopathological analysis in case of recurrence or metastasis for individualized therapy planning. Further studies with larger case numbers are necessary to validate our findings.