Endometrial carcinomas with mismatch repair deficiency: immunophenotypical and molecular characterization.

This project was focused on the molecular and immunophenotypical characterization of a series of 80 gynecological cancers (GC, 64 endometrial, 12 ovarian, 4 endocervical) from patients who referred to the Cancer Genetic Counseling of Varese Hospital. We investigated the immunohistochemical (IHC) expression of MMR proteins, the microsatellite (MSI) profile of GC. We observed that the IHC analysis identified more cases with MMR deficit respect to the MSI analysis, in particular we identified a subgroup of cases with a borderline MSI profile. In order to improve MSI test, we tested four additional MSI target loci (RPL22, SRPR, MBD6 and NRIP) by setting up the MSI test in our series, these analysis revealed RPL22 and SRPR as informative loci in borderline cases and provided MSI evaluation criteria. We also analyzed MLH1 promoter methylation profile in MLH1 IHC negative samples to distinguish the sporadic MLH1 negative samples to LS cases. We set up the IHC analysis of ARID1A protein. We observed ARID1A protein loss in LS cancers, respect to sporadic cancer. Finally, we investigated the mutational landscape of 16 genes involved in endometrial cancer by targeted exome sequencing in 35 endometrial cancers. The genes most frequently mutated were ARID1A, ARID2, PTEN. The MSI cases show a higher mutational rate respect to MSS samples.