Abstract 474: Tumor CD57+ immune cell infiltration is a strong independent prognostic factor in stage II-III colorectal cancer

Abstract

Abstract Background: CD3+ CD45RO+ tumor infiltrating lymphocytes (TIL) density within colorectal cancer (CRC) has been shown to be a better predictor of outcome than UICC TNM. Conversely, Laghi and coll. showed that CD3+ TIL density was not a prognostic factor in stage III CRC. The aim of our study was to evaluate the prognostic role of immune infiltrating tumor cells in stage II and III CRC patients using a tissue microarray (TMA) analysis. Methods: A tissu-array was constructed using 202 stage II and III resected CRC (154 CC, 48 rectal cancers) and their matched non tumor tissue (NT). Tumors exhibiting deficient mismatch repair phenotype have been excluded. On the basis of previous data on the prognostic role of immune response in CRC, the following stainings were quantified in tumor (TT) and NT: CD3, CD68, CD57, CD8 and CD4 in order to quantify macrophage, lymphocyte cell infiltration as effectors of IFN-γ production, CXCL9/MIG, PPAR γ, CXCL10/IP-10, INDO, CXCL13/BCA-1. For prognostic analysis, immunohistochemistry (IHC) data was dichotomized at the median value. Results: All proteins (except CXCL10/IP-10, INDO for which no reliable IHC data could be obtained) were significantly underexpressed in TT as compared to NT (p<0.0001, paired t-test). CD57 expression was significantly correlated with both CD3 and CD8 expression in TT (Spearman rank correlation coefficients equal to 0.41 (p<0.001) and 0.22 (p=0.002) respectively). After the exclusion of patients who received preoperative irradiation for rectal cancer (n=38), and after adjustment for tumor stage, adjuvant chemotherapy and tumor site in Cox models, CD3 and CD57 tumor staining were associated to recurrence-free survival (RFS) (HR=0.48 and 0.33 and p-value=0.02 and 0.003 respectively) whereas none of the NT staining was found to be prognostic. When CD3 and CD57 tumor staining were included together in the Cox model, only CD57 remained significantly associated with RFS (HR=0.37, p=0.015), especially in stage III CRC but without statistically significant interaction between stage and CD57. Conclusion: Tumor CD57+ immune cell infiltration is associated with prolonged recurrence-free survival in stage II and III colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 474. doi:10.1158/1538-7445.AM2011-474