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Endometrial cancer
2022-RA-1289-ESGO Understanding clinical and pathological heterogeneity of endometrial cancer with no specific molecular profile (NSMP)
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  1. Luigi Antonio de Vitis1,
  2. Gabriella Schivardi1,2,
  3. Caterina Fumagalli3,4,
  4. Benedetta Zambetti1,
  5. Mariacristina Ghioni5,
  6. Paola Rafaniello Raviele5,
  7. Alessandra Rappa5,
  8. Maria Teresa Achilarre1,
  9. Alessia Aloisi1,
  10. Annalisa Garbi1,
  11. Mariateresa Lapresa1,
  12. Gabriella Parma1,
  13. Vanna Zanagnolo1,
  14. Giovanni Damiano Aletti1,6,
  15. Andrea Mariani2,
  16. Angelo Maggioni1,
  17. Massimo Barberis5,
  18. Nicoletta Colombo1,7,
  19. Francesco Multinu1 and
  20. Ilaria Betella1
  1. 1Department of Gynecology, European Institute of Oncology, Milan, Italy
  2. 2Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN
  3. 3Clinical Unit of Oncogenomics, European Institute of Oncology, Milan, Italy
  4. 4Department of Diagnostic Services, Division of Pathology, ASST Valle Olona, Gallarate, Italy
  5. 5Department of Pathology, European Institute of Oncology, Milan, Italy
  6. 6Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
  7. 7Faculty of Medicine and Surgery, University of Milan Bicocca, Milan, Italy

Abstract

Introduction/Background No-specific molecular profile (NSMP) endometrial cancers (ECs) lack a unique molecular feature and show considerable molecular heterogeneity. However, CTNNB1 hotspot mutations have been associated with adverse outcomes. The aim of the study is to explore molecular features of NSMP-ECs and to investigate the role of CTNNB1.

Methodology Among all ECs undergoing molecular analysis at the European Institute of Oncology, Milan, between April 2019 and December 2021, NSMP-ECs were identified. The molecular profiling included MMR-proteins and p53 immunohistochemistry, microsatellite instability evaluation and Next Generation Sequencing of 26 cancer-related genes, including POLE, TP53 and CTNNB1. NSMP-ECs were classified according to CTNNB1 status. Clinicopathological characteristics between CTNNB1-mutated and CTNNB1-wild-type ECs were compared. To compare continuous and categorical variables Mann-Whitney test and chi-square test were used, respectively.

Results Overall, 124 (44.6%) NSMP-ECs were identified among the 278 ECs that underwent complete molecular analysis. Clinicopathological and molecular characteristics of NSMP-ECs are shown in figure 1.

The majority of NSMP-ECs were endometrioid (n=121, 97.6%), low-grade (n=107, 86.3%), FIGO stage I (n=82, 66.1%), with no/focal lymphovascular space invasion (n=119, 96.0%) and with <50% myometrial invasion (n=85, 68.5%). According to the ESGO/ESTRO/ESP guidelines, 52.4% (n=65) were low-risk ECs.The most commonly mutated genes were PTEN (n=82, 66%), CTNNB1 (n=48, 39%), PIK3CA (n=39, 31%) and KRAS (n=27, 22%). CTNNB1 and KRAS mutations were mutually exclusive (p<0.001).CTNNB1-mutated were younger (55.3±12.9 vs 63.2±12.3, p=0.002) than CTNNB1 wild-type. Histotype, myometrial invasion, lymphovascular space invasion, grade, stage, and ESGO/ESTRO/ESP risk class did not differ between the two groups (table 1).

Abstract 2022-RA-1289-ESGO Figure 1
Abstract 2022-RA-1289-ESGO Figure 1
View this table:
Abstract 2022-RA-1289-ESGO Table 1

Clinicopathological characteristics comparison between CTNNB1 wild type and mutated NSMP endometrial cancers

Conclusion Our study confirms the high prevalence of PI3K/AKT/mTOR and Wnt pathways alterations in NSMP-ECs and the mutually exclusive pattern between CTNNB1 and KRAS. Mutations in CTNNB1 occur in younger patients, but do not imply different clinicopathological characteristics.

https://doi.org/10.1136/ijgc-2022-ESGO.301

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