title: Are prediction models for Lynch syndrome valid for probands with endometrial cancer?
abstract: Currently, three prediction models are used to predict a patient's risk of having Lynch syndrome (LS). These models have been validated in probands with colorectal cancer (CRC), but not in probands presenting with endometrial cancer (EMC). Thus, the aim was to determine the performance of these prediction models in women with LS presenting with EMC. Probands with EMC and LS were identified. Personal and family history was entered into three prediction models, PREMM(1,2), MMRpro, and MMRpredict. Probabilities of mutations in the mismatch repair genes were recorded. Accurate prediction was defined as a model predicting at least a 5% chance of a proband carrying a mutation. From 562 patients prospectively enrolled in a clinical trial of patients with EMC, 13 (2.2%) were shown to have LS. Nine patients had a mutation in MSH6, three in MSH2, and one in MLH1. MMRpro predicted that 3 of 9 patients with an MSH6, 3 of 3 with an MSH2, and 1 of 1 patient with an MLH1 mutation could have LS. For MMRpredict, EMC coded as "proximal CRC" predicted 5 of 5, and as "distal CRC" three of five. PREMM(1,2) predicted that 4 of 4 with an MLH1 or MSH2 could have LS. Prediction of LS in probands presenting with EMC using current models for probands with CRC works reasonably well. Further studies are needed to develop models that include questions specific to patients with EMC with a greater age range, as well as placing increased emphasis on prediction of LS in probands with MSH6 mutations.
authors.affiliation: The Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210-1228, USA.
authors.forename: Floor J
authors.initials: FJ
authors.lastname: Backes
authors.forename: Heather
authors.initials: H
authors.lastname: Hampel
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Backes
authors.forename: Luis
authors.initials: L
authors.lastname: Vaccarello
authors.forename: George
authors.initials: G
authors.lastname: Lewandowski
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bell
authors.forename: Gary C
authors.initials: GC
authors.lastname: Reid
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Copeland
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Fowler
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015233:Models, Statistical; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011336:Probability; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein