From the Department of Medical Oncology, Hospital Vall d’Hebron, Medical Department Universitat Autònoma de Barcelona, Spain; Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands; Division of Gastroenterology, Brigham and Women's Hospital, Population Sciences Division, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Judith Balmaña, MD, Medical Oncology Department, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain, Ph: 34-93-2746085; e-mail: jbalmana{at}vhebron.net
Overview: Several predictive models for identification of germ-line mutation carriers in Lynch syndrome have been developed. Up to now, initial identification of individuals at risk for Lynch syndrome was based on fulfillment of clinical criteria (i.e., the Amsterdam criteria or the Bethesda guidelines); subsequent evaluation included molecular screening of tumors by analysis of mismatch repair deficiency with microsatellite instability or loss of expression of the corresponding protein with immunohistochemistry. Predictive models in Lynch syndrome may represent a new quantitative tool to help identify its presence, communicate risk, and guide molecular evaluation in individuals at risk. The three most relevant models — the Barnetson et al, PREMM1,2, and the MMRpro — were recently developed in different study populations but have not yet been validated in the same group. Individual comparisons of their performance with clinical criteria suggest that any of these models may work similarly to or better than the Bethesda guidelines/Amsterdam criteria. Nevertheless, translation of specific predicted risks into clinical decision making requires further validation in external study populations to warrant well-calibrated cutoffs and transportability to different settings.
