1. Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study
- Author
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Thomas C. Smyrk, Paul J. Limburg, Anne Marie O'Shea, Steven Gallinger, Michael Walsh, Polly A. Newcomb, Paul Waring, Andrew Ruszkiewicz, Mark Redston, Aaron Pollett, Robert W. Haile, Melissa A. Barker, Lawrence J. Burgart, Shinichi Hayashi, John L. Hopper, Joanne P. Young, Graham G. Giles, James G. Dowty, Mark A. Jenkins, John D. Potter, David Shimizu, John A. Baron, Jeremy R. Jass, Loic LeMarchand, Noralane M. Lindor, Stephen N. Thibodeau, and Graham Casey
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Male ,Pathology ,medicine.medical_specialty ,Colorectal cancer ,Population ,Medical Oncology ,MLH1 ,Article ,Predictive Value of Tests ,medicine ,Humans ,education ,Probability ,education.field_of_study ,Models, Genetic ,Hepatology ,business.industry ,Gastroenterology ,Reproducibility of Results ,Microsatellite instability ,DNA, Neoplasm ,Odds ratio ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Lynch syndrome ,Confidence interval ,Predictive value of tests ,Practice Guidelines as Topic ,Female ,Microsatellite Instability ,business - Abstract
The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H).Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H.Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9-14.1), proximal subsite (OR, 4.7; 95% CI, 3.1-7.3), mucinous histology (OR, 2.8; 95% CI, 1.7-4.8), poor differentiation (OR, 1.9; 95% CI, 1.2-3.1), Crohn's-like reaction (OR, 1.9; 95% CI, 1.2-2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3-2.9). MsPath scoreor=1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H.The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years.
- Published
- 2007
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