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.