Combination of microsatellite instability and lymphocytic infiltrate as a prognostic indicator in colon cancer.

BACKGROUND Microsatellite instability (MSI) is a genetic aberration associated with less aggressive tumor biology. Some tumors with MSI also have lymphocytic infiltrate (LI), which suggests a heightened immune response against the tumor. OBJECTIVE To evaluate the combined prognostic significance of MSI and LI in a colon cancer population. DESIGN Colon cancers were prospectively evaluated for MSI by assessing 11 satellite markers and were classified as MSI+ if 2 or more satellite markers displayed instability. Tumors were classified as LI+ if at least 5 lymphocytes were observed per 10 high-power fields. SETTING Community hospital system. PATIENTS Individuals undergoing definitive surgery for colon cancer. MAIN OUTCOME MEASURES Overall and disease-free survival were compared according to combined MSI and LI status. RESULTS In 150 patients, tumors were classified as follows: 95 were MSI-/LI-, 9 were MSI-/LI+, 30 were MSI+/LI-, and 16 were MSI+/LI+. Median follow-up was 40.6 months. Five-year disease-free survival was 56.7% for patients with MSI-/LI- tumors and 88.9% for those with MSI+/LI+ tumors (P = .01). Patients with MSI+/LI- and MSI-/LI+ tumors had 5-year survival of 75.4% and 75.0%, respectively. CONCLUSIONS Patients with colon cancer and MSI-/LI- tumors have worse disease-free survival rate regardless of stage at diagnosis. Patients exhibiting both MSI+ and LI+ tumors have more favorable disease-free survival rates. Both MSI and LI show promise as a combined prognostic marker and with further study may prove to be particularly useful in selecting patients with stage II disease for adjunctive therapy.