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Type: Journal article
Title: Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: A population-based study
Author: Jenkins, M.
Hayashi, S.
O'Shea, A.
Burgart, L.
Smyrk, T.
Shimizu, D.
Waring, P.
Ruszkiewicz, A.
Pollett, A.
Redston, M.
Barker, M.
Baron, J.
Casey, G.
Dowty, J.
Giles, G.
Limburg, P.
Newcomb, P.
Young, J.
Walsh, M.
Thibodeau, S.
et al.
Citation: Gastroenterology, 2007; 133(1):48-56
Publisher: W B Saunders Co
Issue Date: 2007
ISSN: 0016-5085
Abstract: Background & Aims: 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). Methods: 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. Results: 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 score ≥1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. Conclusions: 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 score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years.
Keywords: Colon Cancer Family Registry
Colorectal Neoplasms, Hereditary Nonpolyposis
DNA, Neoplasm
Reproducibility of Results
Predictive Value of Tests
Medical Oncology
Models, Genetic
Middle Aged
Microsatellite Instability
Practice Guidelines as Topic
Description: Copyright © 2007 AGA Institute Published by Elsevier Inc.
DOI: 10.1053/j.gastro.2007.04.044
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Pathology publications

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