CRC of patients with Lynch syndrome shows MMR deficiency, defined by the presence of microsatellite instability (MSI) and loss of the MMR protein expression, which is the hallmark of this disorder [3]. The syndrome accounts for 2%–4% of all CRCs and the lifetime risk of developing CRC in the MMR mutation carriers is estimated to be 50%–80% [4, 5]. Therefore, Dorsomorphin nmr patients with LS and their relatives have to undergo intensive surveillance and appropriate management to improve

their survival [6–8]. The most widely used diagnostic strategy for Lynch syndrome is based on selecting patients who fulfil the Amsterdam criteria [2] or any of the Revised Bethesda Guidelines [9], followed by Tumour (Tissue) Testing of MSI and/or immunostaining (IHC) of MMR proteins and germline mutation analysis in MMR deficient cases. The Amsterdam

Criteria allow to select patients on the basis of familial segregation and early age at onset of CRC or other cancer in LS spectrum. The Revised Bethesda Guidelines are less stringent and consider age at onset, presence of synchronous/metachronous cancer (multiple primary cancer), MSI-H phenotype at age < 60 years and familial history of cancer in LS spectrum separately. Both clinical criteria emphasize the importance of early age at onset (≤ 50 years) to suspect LS. Furthermore, recent findings suggest an increasing incidence of CRC in young patients [10–12] as well as the association with advanced stage, prevalent distal location and poor prognosis [10, 13–19]. Therefore, patients with CRC at age ≤ 50 yrs Selleck EX-527 have been considered for LS screening in several studies and the prevalence of LS in early onset-CRC cohorts resulted extremely variable accounting for about 5% to 20% [13, 20–32]. The heterogeneity learn more of the results of these studies is likely due to different methodological approaches, kind of cohort studied and different molecular strategies used for detecting LS. The variability of molecular

strategies reflects that, at present there is considerable uncertainty regarding whether to recommend IHC or MSI or the combination of both as a primary screening tool [33–35]. Some authors found a similar effectiveness of both techniques to screen LS, but consider IHC less complex and suggest to start with it [33]. The recent Jerusalem Workshop [34] recommended to use IHC or MSI alternatively, whereas the last revised NCCN guidelines [35] propose to use a combination of both as testing strategies for LS in high risk subjects. The primary aim of our study was to evaluate the prevalence of Lynch syndrome in a single-center large series of early-onset CRC without family history compared with those with family history of CRC and/or other malignancies of LS spectrum.