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

BACKGROUND: Microsatellite instability (MSI) and lymphocytic infiltrate (LI) in colon cancer are associated with less aggressive biological characteristics. Patients with stage II disease who are negative for MSI and LI have been found to have a less favorable prognosis. These patients may be candidates for more aggressive adjuvant therapy. OBJECTIVE: To evaluate the outcomes of patients with colon cancer treated with and without adjuvant chemotherapy on the basis of stage, MSI, and LI. DESIGN: Prospective evaluation of MSI and LI status with retrospective analysis of chemotherapy regimen. SETTING: Community hospital system. PATIENTS: A total of 167 patients with colon cancer. INTERVENTION: Definitive resection of colorectal cancer with or without chemotherapy. Main Outcome Measure Disease-free survival (DFS) with and without chemotherapy according to combined MSI and LI status. RESULTS: Data on MSI and LI status and chemotherapeutic regimens were available for 140 patients. The 5-year DFS was 50% for patients with stage II disease who underwent chemotherapy vs 76% for those who did not (P = .02). In the group negative for MSI and LI, 5-year DFS was 29% for those undergoing chemotherapy and 91% for those who did not (P = .001). CONCLUSIONS: Forgoing adjuvant chemotherapy should be considered in patients with stage II colon cancer who are negative for MSI and LI. The MSI and LI status shows promise as a combined prognostic marker and may prove particularly useful in selecting patients with stage II disease for adjunctive therapy.

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.

A prospective analysis of microsatellite instability as a molecular marker in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) may be a molecular marker of colorectal tumor biology. We sought to evaluate the incidence and significance of MSI in an unselected colorectal cancer population. METHODS: Colorectal cancer cases from a community health system were prospectively evaluated for MSI and patient outcomes monitored. RESULTS: Of 240 eligible, 140 underwent testing; 43 (31%) had high-frequency MSI (MSI-H). Those with MSI-H tumors presented with earlier disease stage (P = .014) and lymphocytic infiltration (P < .001). Stage III MSI-H patients trended toward improved disease-free survival (P = .065). MSI-H patients were more likely to have other primary malignancies. CONCLUSIONS: Prevalence of MSI-H in the general colorectal cancer population is higher than previously reported. MSI testing of colorectal cancers is useful as part of a molecular profile to stratify patients for prognosis, treatment, and further study. Patients with MSI-H tumors are more likely to have other primary malignancies, suggesting a role for heightened screening.