Cells with deficient DNA mismatch repair develop microsatellite instability. Extensive microsatellite instability (MSI‐high) is characteristic of colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma (HNPCC) and in 10–% 15% of sporadic colorectal carcinomas. Microsatellite instability‐high colorectal carcinomas differ from others in important clinical and pathologic features. However, MSI typing is expensive and not widely available. Microsatellite instability type may be predicted by tumor‐infiltrating lymphocytes (TILs), which can be evaluated with ordinary light microscopy.

The authors evaluated TILs as a pathology screen for MSI‐high status in 138 colorectal carcinomas that had been evaluated for MSI in a variety of studies. This case series was systematically enriched with HNPCC and other MSI‐high cases to allow accurate sensitivity and specificity estimation. Tumor‐infiltrating lymphocytes were quantitated as TILs per 10 high‐power microscopic fields by an observer blinded to MSI status.

Of the 138 carcinomas studied, 67 (48.6%) were MSI‐high, 22 (15.9%) were MSI‐low, and 49 (35.5%) were MSI‐stable. All 25 HNPCC colorectal carcinomas were MSI‐high. Tumor‐infiltrating lymphocytes counts ranged from 0 to 300, with a markedly skewed distribution (median, 11; mean, 36). Sensitivity and specificity for selected cut points of TIL count were computed. Using a TIL count of 5 as a cut point yields a sensitivity of 93% and specificity of 62%. In a population in which 12% were MSI‐high, consideration of TIL could reduce the number of colorectal carcinomas referred for MSI testing by greater than one‐half, and still 93% of the MSI‐high carcinomas would be identified.

The presence of MSI defines a subset of colorectal carcinomas with special molecular etiology and characteristic clinical, pathologic features, inclusive of increased survival. The authors conclude that quantification of TILs may provide a simple, single criterion for choosing which colorectal carcinomas are candidates for MSI testing. Cancer 2001;91:2417–22. © 2001 American Cancer Society.