Lymphoid Reaction to Colorectal Cancer Predicts Patient Survival Independent of Lymph Node Count and MSI, and Explains the Association between CIMP and Good Prognosis
S Ogino, K Nosho, JN Glickman, M Mino-Kenudson, CS Fuchs. Brigham and Women's Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts General Hospital, Boston, MA
Background: Host immune response to tumor may be an important prognostic factor for colon cancer patients. However, little is known on prognostic significance of histopathologic lymphoid reaction, independent of the lymph node count and tumoral molecular alterations, both of which are associated with lymphocytic reaction and prognosis.
Design: Among 843 colorectal cancers, we examined 4 components of lymphocytic reaction (0-3) (i.e., Crohn's-like reaction, peritumoral reaction, intratumoral periglandular reaction and tumor infiltrating lymphocytes) and an overall lymphocytic reaction score (0-12). We used Cox regression to compute hazard ratio (HR) for mortality, adjusted for clinical and tumoral characteristics, including the positive and negative lymph node counts, microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and KRAS and BRAF mutations.
Results: Increasing overall lymphocytic reaction score was associated with a significant improvement in colorectal cancer-specific and overall survival (log-rank p<0.003).
In multivariate analysis, middle (3-6) and high (7-12) lymphocytic scores were associated with improved overall survival [multivariate HR, 0.71; 95% confidence interval (CI) 0.54-0.93; multivariate HR 0.49; 95% CI 0.28-0.86, respectively; p for trend=0.002]. The beneficial effect of CIMP was attenuated when adjusting for lymphocytic score, implying that lymphocytic reaction explain the relation between CIMP and good prognosis.
Conclusions: Lymphocytic reaction to colorectal cancer predicts improved survival, independent of the lymph node count and molecular features.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 75, Tuesday Afternoon