Exploring endometrial cancer risk stratification by copy number assessment

Contemporary management of endometrial cancer includes molecular classification. The primary objective of this study was to assess the prognostic significance of copy number changes evidenced by loss of heterozygosity (LOH) or allelic imbalance (AI).

Sequencing including TP53, POLE and MSI testing was performed. AI/LOH at 5 polymorphic markers (D2S123, D5S2346, D17S250, D17S516 and D17S1818) was assessed. Micro-satellite stable (MSS) endometrial tumors were classified as having evidence of AI/LOH or no evidence of AI/LOH.

482 MSS cases were evaluated for AI/LOH status. There were 226 (46.5 %) tumors with evidence of AI/LOH at ≥1 of the 5 markers and these were significantly associated with patients of older age and lower body mass index as well as tumors that were non-endometrioid histology, higher grade, demonstrated LVSI, and presented at more advanced stage. Most patients who developed recurrent disease had a tumor with AI/LOH (82.1 %). 3-year progression-free survivals (PFS) were 79.5 % in the AI/LOH group vs 95.6 % in the no AI/LOH group (p < 0.0001). TP53 mutation status was associated with PFS. 3-year PFS was significantly worse for the TP53 mutated group at 55 % vs 96 % in TP53 wild-type (p < 0.0001). Of the 373 cases classified as having no specific molecular profile there was a 6.2 % recurrence rate with AI/LOH and 3.3 % recurrence with no AI/LOH.

AI/LOH assessment at a limited number of markers identifies endometrial cancers with higher risk features that are more likely to recur. Copy-number assessment utilizing clinically accessible testing strategies can provide an opportunity for improved risk stratification.