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.