First results of universal screening for Lynch syndrome in a Mexican cohort of colorectal cancer patients.

Abstract

590 Background: universal screening has been proposed as an alternative to clinical criteria for detection of Lynch syndrome (LS). Results of such policy have not been evaluated in mexican population with low incidence of colo-rectal cancer (CCR). Objective: to determine the proportion of patients tested by immunohistochemistry (IHC) for mismatch repair-deficient (dMMR) and characterize subsequent molecular and clinical work up for abnormal results. Methods: we identified all consecutive cases of CCR during 2016 at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico. We recorded clinical variables, IHC for mismatch repair (MMR) proteins and/or clinical genetics evaluation and molecular confirmation of LS if available. Results: universal screening policy was adopted by our institution in 2016. 209 CRC patients had an outpatient consultation. The median age at diagnosis was 59.8 years. 103 IHC for MMR proteins were done (49%) regardless of age at diagnosis and a family history of CRC. 36/103 (35%) IHC showed abnormal result meaning lack of expression of at least one of four MMR proteins: 26 MLH1, 7 MSH2, 10 MSH6 and 23 PMS2. 11/36 patients (30%) had a family history of CRC. 26/36 (72%) were evaluated by clinical genetics service. Of 26 MLH1 deficient patients, only one case was tested for BRAF mutation. 14/36 patients (39%) were tested by sequencing analysis: 7 MLH1, 5 MSH2, 1 MSH6, 1 PMS2. 2/14 patients were tested by MLPA assay given negative sequencing analysis. Germ-line mutations were identified in 7/36 patients (19%). All mutations were identified in patients with a clinical suspicion given strong family history of CRC. No identified mutations could be attributed to universal screening policy. Conclusions: during the first year of implementing universal screening for LS in CRC patients only half of the patients were screened by IHC. Despite MLH1/PMS2 deficiency was the most frequent abnormality, BRAF mutation analysis was not performed as recommended, given the lack of access to the test. A clinical suspicion of LS was a determinant driver for confirmatory molecular testing therefore limiting the usefulness of universal screening.