TY - JOUR
T1 - Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability
T2 - A Population-Based Study
AU - Jenkins, Mark A.
AU - Hayashi, Shinichi
AU - O'Shea, Anne Marie
AU - Burgart, Lawrence J.
AU - Smyrk, Tom C.
AU - Shimizu, David
AU - Waring, Paul M.
AU - Ruszkiewicz, Andrew R.
AU - Pollett, Aaron F.
AU - Redston, Mark
AU - Barker, Melissa A.
AU - Baron, John A.
AU - Casey, Graham R.
AU - Dowty, James G.
AU - Giles, Graham G.
AU - Limburg, Paul
AU - Newcomb, Polly
AU - Young, Joanne P.
AU - Walsh, Michael D.
AU - Thibodeau, Stephen N.
AU - Lindor, Noralane M.
AU - LeMarchand, Loïc
AU - Gallinger, Steven
AU - Haile, Robert W.
AU - Potter, John D.
AU - Hopper, John L.
AU - Jass, Jeremy R.
N1 - Funding Information:
Supported by the National Cancer Institute, National Institutes of Health, under RFA #CA-95-011 and through cooperative agreements with the Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806), as well as R01 CA74806, U01-CA74800, and CA74778.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
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U2 - 10.1053/j.gastro.2007.04.044
DO - 10.1053/j.gastro.2007.04.044
M3 - Article
C2 - 17631130
AN - SCOPUS:34447251079
SN - 0016-5085
VL - 133
SP - 48
EP - 56
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -