Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma

Thomas C. Smyrk, Patrice Watson, Karen Kaul, Henry T. Lynch

Research output: Contribution to journalArticle

326 Scopus citations

Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)2417-2422
Number of pages6
JournalCancer
Volume91
Issue number12
DOIs
StatePublished - Jun 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma'. Together they form a unique fingerprint.

  • Cite this