OR02: The LynCE study (The pilot): An assesment of endometrial cancer progression markers in Lynch syndrome

Rosa Guarch Troyas1,2, Mar Arias Alonso2, Sira Moreno Laguna1,2, Eva Recari Elizalde1,2, Angel Alonso Sánchez1,2*

1 – Complejo Hospitalario de Navarra, 2 – Oncogenetics and Hereditary Cancer Group. IDISNA (Biomedical Research Institute of Navarre)

Aim

Abnormal Mismatch Repair (MMR) proteins Inmunohistochemistry (IHC) and Microsatellite Instability (MSI) has been observed both in tumoural and normal endometrial biopsies in patients carrying mutations predisposing to Lynch syndrome (LS). The potential use of these findings as potential makers for progression to endometrial cancer is to be clarified in a prospective multicentric study: the LynCE study. These are the results of its pilot study.

Method

Material:

  • 72 endometrial biopsy samples from 51 Lynch Syndrome (LS) carriers: (MLH1=22; MSH2=21; MSH6=8), with different pathology diagnoses: Normal Endometrium (NELS=34); Complex Endometrial Hyperplasia (CEHLS=4) and Endometrial Carcinoma (ECLS= 13).
  • 17 Normal Endometrium biopsies from control population (NEC=17).

Methods: IHC (MMR), MSI. Survival analysis; Endpoint= progression to endometrial cancer.

Results

•100% (13/13) of the Endometrial Cancer (ECLS) and Endometrial Hyperplasias (CEHLS) (4/4) in Lynch syndrome patients showed absent IHC concordant with the underlying genetic defect, and 75% of ECLS and 83% of CEHLS had MSI.

  • 44% (19/34) of Normal Endometrium biopsies from Lynch patients (NELS) and 0% of control population (NEC) showed abnormal IHC (χ² p<0.01**), and 11% (4/34) of NELS vs 0% (0/17) of NEC showed MSI (χ² p=0.14NS).
  • 46% (7/15) of LS carriers whose biopsy showed normal endometrium (NELS) with abnormal IHC, progressed to endometrial cancer (median time=38,4 months) vs 0% (0/19) of those with normal IHC (Log-Rank; Kaplan Meier p<0.001**).
  • 100% (4/4) of LS carriers whose biopsy showed normal endometrium (NELS) with MSI progressed to endometrial cancer (median time=32 months) vs 10% (3/30) of those with MSE (Log-Rank; Kaplan Meier p<0.001**).

Conclusion

Abnormal MMR IHC and MSI is an abnormal finding in normal endometrium biopsies from Lynch Syndrome patients. In the pilot study these markers were able to predict the progression to endometrial cancer. A multicentric study, the LynCE, is now on its way to prospectively validate these results which could improve the medical evidence for recommendations (surveillance vs. prophylactic hysterectomy) in Lynch syndrome patients.

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