N35: An Assessment Of Endometrial Cancer Risk Markers In Lynch Syndrome Patients

A. Alonso1, R. Guarch1, S. Moreno1, E. Recari1, M. Miranda1, I. Chirivella2, E. Lastra3, L. Robles4

1 – Complejo Hospitalario Navarra. 2 – Hospital Clínico Universitario de Valencia. 3 – Hospital Universitario de Burgos. 4 – Universitario 12 Octubre Madrid.


Aim: Assesment of a set of markers to anticipate endometrial cancer occurence in healthy female Lynch syndrome (LS) carriers.

Method: Materials: 242 biopsy specimens obtained during the prospective annual follow-up of 79 Lynch syndrome (LS) carriers from 4 different Spanish Centers.

Investigated markers were (High Microsatellite Instability MSI-H; abnormal mismatch repair proteins  (MMR-IHC) or PTEN (PTEN-IHC) inmunohistochemistry; LINE sequences (LINE-CIN) or MMR genes CpG islands abnormal methylation (MMR-MMR), and somatic mutations in a custom panel of 27 genes related to type 1 endometrial carcinogenesis (Panel-27).

Results: Simultaneous presence of abnormal MMR and PTEN-IHC anticipated the occurrence of the precursor lesion “focal hyperplasia” in a median time of 19,63 months (CI95=17,55-21,71) with a Hazard Ratio HR= 3,97 (CI95=1,32-11,9) vs the no markers group. Panel-27 somatic mutations rate was also higher (75×10-6 mutations per Mb  vs. 12×10-6 mutation per Mb, p<0,05) in these samples.

Conclusion: These findings provide a basis for recommending to introduce the investigation of these markers in biopsy specimens from LS patients, as a supportive tool for selecting the most appropriate management option in these patients (prophylactic hysterectomy vs surveillance).