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: Joel K Greenson, Shu-Chen Huang, Casey Herron, Victor Moreno, Joseph D Bonner, Lynn P Tomsho, Ofer Ben-Izhak, Hector I Cohen, Phillip Trougouboff, Jacob Bejhar, Yanina Sova, Mila Pinchev, Gad Rennert, Stephen B Gruber
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 33 Issue 1 Pg. 126-33 (Jan 2009) ISSN: 1532-0979 [Electronic] United States
• PMID: 18830122 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Topics

• Adenocarcinoma (genetics, pathology)
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Area Under Curve
• Colorectal Neoplasms (genetics, pathology)
• Female
• Humans
• Lymphocytes, Tumor-Infiltrating (pathology)
• Male
• Microsatellite Instability
• Middle Aged
• ROC Curve
• Regression Analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity