Tumor-Infiltrantig Lymphocytes Density as Determinant in Early Stage Colorectal Cancer Prognosis: A Single Centre Pilot Study

Cristiana Lo Nigro,Elena Fea,Cristina Granetto,Mirella Fortunato,Vincenzo Ricci,Marco Carlo Merlano,Teresa Fabozzi,Daniela Vivenza

doi:10.31487/j.rco.2019.01.02

Abstract

Stage II colon cancer (CC) is a heterogeneous disease with different clinical behaviour. There is a high degree of uncertainty in recommending adjuvant chemotherapy, which is usually suggested in the high-risk population on the basis of TNM, stage and key biological markers. Published data suggest that specific tumor-infiltrating lymphocytes (S-TILs) (CD3+, CD8+, CD45RO+) may represent a valuable prognostic tool to drive the decision-making process. We performed an analysis on 13 cases of stage II and III CC that relapsed, and on 15 cases that did not. We analyzed the density of CD3+, CD8+ and CD45RO+ in the surgical samples after radical surgery by IHC in the center of the tumor (CT) and in its invasive margin (IM). 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. This analysis was carried out stratifying patients in two cohorts: stage II (12 patients) and stage III (16 patients). Density of CD3+, CD8+ and CD45RO+ in CT did not affect DFS and OS, except for OS in stage II pts for CD3+ (P=0.012). Conversely HD of CD3+, CD8+ and CD45RO+ in IM showed significant benefit in DFS compared to LD (P=0.001, P=0.013 and P=0.001 respectively) in stage II patients and, only for CD3+, also in stage III patients (P=0.048). Similarly, we observed a significant gain in OS in pts with HD CD3+ and CD45RO+ (P=0.05 and P=0.003) but not CD8+ (P=0.25) in IM for stage II patients. S-TILs might represent a valuable prognostic tool to drive the decision-making process especially for stage II CC disease, with a more pronounced role of S-TILs in IM compared to CT. Our results will be verified in ongoing large prospective study.

Highlights

Colorectal cancer (CC) is one of the so called “big killers”
We aimed to perform a pilot monocentric study on stage II and III CC in order to evaluate the role of tumor-infiltrating lymphocytes (TILs) in CC as independent prognostic marker, over the TNM staging and irrespective of the microsatellite instability (MSI) status
CD3+, CD8+ and CD45RO+ density in center of the tumor (CT) did not correlate with DFS nor overall survival (OS) (Figure 1, 2), with the exception of CD3+ and OS in stage II patients (P=0.012) (Figure 3)

Summary

Introduction

Colorectal cancer (CC) is one of the so called “big killers”. The anatomic extension of the cancer has been the principal prognostic factor. Density, type and the place of immune cells in CC could represent a greater prognostic indicator, irrespective of the anatomic extent of the tumor. As with other solid tumors, staging is based on histopathologic criteria of tumor invasion (T), diffusion to local lymph nodes (N), distant metastases (M) and tumor cell differentiation. According to the tumor stage, the possibility of relapse is different. The involvement of positive lymph nodes (TNM stage III) predicts a 50% to 60% possibility of relapse within 5 years, and requires adjuvant chemotherapy. Stage I-II CCs have a better outcome; 25-30% of those patients develop a disease recurrence [1]

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