Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study.
OBJECTIVE
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 >or=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.
Jenkins
Mark A
MA
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Parkville, Victoria, Australia. m.jenkins@unimelb.edu.au <m.jenkins@unimelb.edu.au>
Hayashi
Shinichi
S
O'Shea
Anne-Marie
AM
Burgart
Lawrence J
LJ
Smyrk
Tom C
TC
Shimizu
David
D
Waring
Paul M
PM
Ruszkiewicz
Andrew R
AR
Pollett
Aaron F
AF
Redston
Mark
M
Barker
Melissa A
MA
Baron
John A
JA
Casey
Graham R
GR
Dowty
James G
JG
Giles
Graham G
GG
Limburg
Paul
P
Newcomb
Polly
P
Young
Joanne P
JP
Walsh
Michael D
MD
Thibodeau
Stephen N
SN
Lindor
Noralane M
NM
Lemarchand
Loïc
L
Gallinger
Steven
S
Haile
Robert W
RW
Potter
John D
JD
Hopper
John L
JL
Jass
Jeremy R
JR
D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005762:Gastroenterology / Q000592:standards*; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000592:standards; D053842:Microsatellite Instability; D008875:Middle Aged; D008957:Models, Genetic; D017410:Practice Guidelines as Topic / Q000592:standards*; D011237:Predictive Value of Tests; D011336:Probability; D015203:Reproducibility of Results
D004273:DNA, Neoplasm