Abstract 502P
Background
Lynch syndrome (LS) is the most prevalent inherited cause of genetic predisposition to colorectal cancer (CRC) by accounting for approximately 1-3% of all newly diagnosed CRC cases. LS includes, beyond CRC, a broad spectrum of associated cancers, with different genetic etiology and risk, including endometrial, gastric, small bowel, ovarian, pancreas, hepato-biliary tract, urinary tract, and brain tumors. Individuals affected by LS show an increased lifetime cumulative risk of CRC (25-80%). The LS is caused by germline pathogenic variants (PVs) in one of four MMR genes, such as MLH1, MSH2, MSH6, PMS2, or in EPCAM gene. The choice of the most suitable criteria and optimal screening strategy for selecting subjects to undergo germline genetic testing are still debated.
Methods
The aim of our work was to evaluate the most suitable selection mode for identifying LS-related CRC patients through different approaches, in order to increase diagnostic power of this hereditary disorder. We retrospectively harvested and analyzed all clinical and pathological information of 854 CRC patients, enrolled at the University Hospital Policlinico “P. Giaccone” of Palermo (Italy), 87 of which were subjected to germline MMR testing based on Amsterdam criteria II and revised Bethesda guidelines, in order to assess the prevalence and typology of different inherited MMR variants detected in LS patients.
Results
Our study revealed that 25 (28.7%) out of 87 CRC patients harboured germline PVs/LPVs in MMR genes, whereas 62 patients were wild-type. No mutation was detected in EPCAM gene. In particular, we found that MSH2 and MLH1 were the more frequently altered genes. MSH2 PVs were mainly associated to CRC women who had developed also endometrial cancers. The best selection approach has proven to be the analysis of tissue microsatellite instability (MSI) status according to the revised Bethesda guidelines.
Conclusions
The use of different approaches of selection is needed for identifying LS-related CRC patients, to reduce underdiagnosis of LS patients. The revised Bethesda guidelines showed a greater diagnostic power compared to Amsterdam criteria II.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University-Hospital Policlinico \"P. Giaccone\", Palermo, Italy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.