title: Pathologic predictors of microsatellite instability in colorectal cancer.
abstract: Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that >2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2>TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (<3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.
authors.affiliation: Department of Pathology, The University of Michigan Health System, Ann Arbor, MI 48109-0054, USA. facjkgmd@umich.edu
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Huang
authors.forename: Casey
authors.initials: C
authors.lastname: Herron
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bonner
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Tomsho
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Izhak
authors.forename: Hector I
authors.initials: HI
authors.lastname: Cohen
authors.forename: Phillip
authors.initials: P
authors.lastname: Trougouboff
authors.forename: Jacob
authors.initials: J
authors.lastname: Bejhar
authors.forename: Yanina
authors.initials: Y
authors.lastname: Sova
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D012372:ROC Curve; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity