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531 Loss-of-heterozygosity as a biomarker for genomic instability and poor outcomes in endometrial cancer
  1. Felix Blanc-Durand1,
  2. Damien Vasseur1,
  3. Patricia Pautier1,
  4. Judith Michels1,
  5. Etienne Rouleau1,
  6. Yi Wan Lim2,
  7. Siew Eng Lim2,
  8. Diana Lim2,
  9. Silvana Wijaya2,
  10. Manavi Sachdeva2,
  11. Natalie Ngoi2,
  12. Benjamin Besse1,
  13. Alexandra Leary1 and
  14. David Sp Tan2
  1. 1Institut Gustave Roussy, Villejuif, France
  2. 2National Cancer Institute, Singapore, Singapore


Introduction/Background Genomic instability has been identified in a subgroup of endometrial cancers (EC) that are predominantly TP53 mutated (TP53mut) with high degree of copy-number alterations. Our objective is to report the features associated with Loss-of-Heterozygosity (LOH) in EC.

Methodology We conducted a retrospective analysis of EC patients from France and Singapore. All patients underwent comprehensive molecular profiling using the tumor-based FoundationOneCDX panel. The degree of LOH was correlated with molecular and clinicopathologic findings. LOH-high, intermediate and low were defined as ≥14%, 4–14%, and <4% respectively.

Results 99 patients were identified, including 62% Asian and 38% Caucasian individuals. 58% had FIGO III/IV diseases, 32% low-grade endometrioid histology, 21% high-grade endometrioid, and 17% serous. 63% and 50% of tumors expressed estrogen (ER) and progesterone receptor (PR) in ≥ 10% tumor cells respectively. 1% had a POLE mutation, 17% were MSI-high, 43% TP53mut and 39% exhibited non-specific molecular profiles. The median LOH was 4.5% (Q1-Q3 1.4–10.5) with 18% patients classified LOH-high, 34% LOH-intermediate and 48% LOH-low.

LOH-High was significantly associated with serous and carcinosarcomas whereas LOH-low with low-grade endometrioid (p<0.001). MSI-high status, ARID1A, PIK3CA, CTNNB1, and PTEN mutations were significantly associated with LOH-low whereas TP53, BRCA1 mutations and TERC amplifications were associated with LOH-high (P<0.05). In particular, all BRCA1mut EC and 38% of the TP53mut were LOH-high. There were significantly more ER and PR-negative cases in the LOH-high subgroup. (p<0.05). The median overall survival was 41.5 months, 55.2 and 100.8 months in the LOH-high, intermediate, and low respectively (P=0.034). Among TP53mut EC, LOH-low patients had significantly poorer outcomes (p<0.001).

Conclusion In this large multiethnic cohort, 18% of EC exhibited high LOH exceeding 14%. Higher LOH was correlated with hormone-receptor-negative tumors and poorer survival rates. LOH may serve as a valuable tool for identifying EC cases with high genomic instability that could potentially benefit from PARP inhibitors.

Disclosures None

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