title: Improved Detection of Microsatellite Instability in Early Colorectal Lesions.
abstract: Microsatellite instability (MSI) occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR) tracts. Adenomas from 160 patients, ranging in age from 29-55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega). This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001), which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001). The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible.
authors.affiliation: Genetic Analysis Group, Promega Corporation, Madison, Wisconsin, United States of America; Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Bacher
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Chelsie K
authors.initials: CK
authors.lastname: Sievers
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Albrecht
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Grimes
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Matkowskyj
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Rashmi M
authors.initials: RM
authors.lastname: Agni
authors.affiliation: Genetic Analysis Group, Promega Corporation, Madison, Wisconsin, United States of America.
authors.forename: Irina
authors.initials: I
authors.lastname: Vyazunova
authors.affiliation: Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Clipson
authors.affiliation: Genetic Analysis Group, Promega Corporation, Madison, Wisconsin, United States of America.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Storts
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Thliveris
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Halberg
mesh_terms: D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf