Research paper: Colorectal cancerUniversal screening to identify Lynch syndrome: two years of experience in a Northern Italian CenterChiaravalli, A.M.a,,b; Carnevali, I.a,,b; Sahnane, N.a,,b; Leoni, E.a; Furlan, D.a,,b,,c; Berselli, M.b,,d; Sessa, F.a,,b,,c; Tibiletti, M.G.a,,bAuthor Information aUO Anatomia Patologica Ospedale di Circolo ASST-Settelaghi Varese bCentro di ricerca per lo studio dei tumori eredo-familiari, Università dell’Insubria Varese cDepartment of Medicine and Surgery, University of Insubria, Varese, Italy dDepartment of Surgery, Surgical Oncology and Minimally Invasive Unit, ASST Settelaghi, Italy Received 25 March 2019 Accepted 6 August 2019 Correspondence to Ileana Carnevali, PhD, BD, Department of Pathology, Ospedale di Circolo, ASST Settelaghi, Via O. Rossi 9, 21100 Varese, Italy, Tel: +39 0332 270601; fax: +39 0332 270600; e-mail: email@example.com European Journal of Cancer Prevention: July 2020 - Volume 29 - Issue 4 - p 281-288 doi: 10.1097/CEJ.0000000000000543 Buy Metrics Abstract Lynch syndrome is caused by germline mutations of genes affecting the mismatch repair proteins MLH1, MSH2, MSH6 or PMS2. Identification of Lynch syndrome patients using germline molecular testing in colorectal cancer (CRC) affected patients and in their healthy relatives is a cost-effective model of cancer prevention. Several studies demonstrate that universal tumor testing using immunohistochemical (IHC) analysis of CRC samples is the most efficient approach to identifying patients affected by Lynch syndrome. We studied a cohort of 352 consecutive CRCs for MSH2, MLH1, MSH6 and PMS2 protein expression using universal IHC screening. IHC mismatch repair (MMR) defects were identified in 70 out of 352 cases (19.8%) including six CRCs MSH2/MSH6 defective, two CRCs, respectively, MSH6 and PMS2 defective, 58 CRCs MLH1/PMS2 defective and four CRCs showing atypical MMR pattern. MLH1 promoter methylation and V600E BRAF mutation analysis were investigated on 61 CRCs. Cancer genetic counseling was offered to all 68 patients affected by MMR defective CRCs and 25 patients opted in to this service (36.8% compliance). Pathogenetic variants of MSH2 genes were identified in two cases (55 and 79 years old). Universal screening based on an IHC approach showed a Lynch syndrome incidence of 1/173. The protocol recommended by regional law improved patient compliance. This study demonstrates that the IHC approach for both MMR deficiency and V600E BRAF mutation detections is the most efficient approach for Lynch syndrome screening in the Italian population. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.