P-269 - Correlation between the prognostic value of tumor-infiltrating lymphocytes (TILS) and sidedness in colorectal cancer (CC) patients (pts)

Abstract

Introduction: Right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC) have a different biology and genomic pattern. Primary tumor location is emerging as an important prognostic factor in metastatic CC patients eligible to target therapy. In a previous work, we have reported that specific tumor-infiltrating lymphocytes (S-TILs) (CD3+, CD8+, CD45RO+) may represent a valuable prognostic tool to drive the decision making-process in stage II colon cancer (CC) disease. In this study we aim to evaluate the relationship and the prognostic impact between TILs and the anatomical subsite (RCC vs LCRC) in primary non metastatic CC, regardless the stage. Methods: We performed a retrospective analysis on 48 CC pts (17F/31M, median age 68.1 - range 52-91 years) underwent adjuvant therapy, of which 33 relapsed and 15 did not, subdivided according to the anatomical sidedness of their primary tumors. We analyzed, by immunohistochemical staining, the density of CD3+, CD8+ and CD45RO + (memory cells) in the center of the tumor (CT) and in its invasive margin (IM) within the surgical tissues samples after radical surgery, comparing them on their primary tumor location. Measurements were recorded by image analysis as the number of positive cells per tissue surface unit in square millimeters. For each marker, we identified two grading of staining, high density (HD) or low density (LD), where the cut-off was the median value observed. Kaplan-Meier analysis was applied to compare the effect of TILs, between HD and LD, on disease free survival (DFS) and overall survival (OS) in the subgroups pts of RCC and LCRC. Due to the small cohort of 48 pts we have not been able to combine the tumor stage II (N = 15) and III (N = 33) with anatomical sidedness, thus this analysis was conducted subdividing patients in 17 RCC and 31 LCRC. Results: When we stratified pts by TILs density for each specific marker (CD3+, CD8+ and CD45RO+) for the anatomical sidedness, HD TILs pts showed a trend in LCRC for a longer OS compared to RCC pts, which became statistically significant for CD45RO+ in CT (p = 0.0061). On the contrary, for the entire cohort of 48 pts no differences in OS and DFS were found between LCRC and RCC pts without stratification for TILs. DFS was significantly improved in LCRC at both IM and CT only in pts with HD CD3+. On the contrary RCC showed DFS benefit only in HD CD45RO+ at IM. OS was significantly improved in LCRC in pts showing HD CD3+ and CD45RO+ at CT. HD CD45RO+ was also significant at IM. No significant differences were observed among CD3+, CD45RO+, CD8+, HD vs LD, in RCC. Conclusion: Specific HD TILs is an important prognostic factor regardless of sidedness of CC tumour; furthermore, in our analysis, the presence of HD CD45RO+ in CT of LCRC is correlated to a better survival.