The Interplay of CD8+ TILs and Microvascular Density: A Novel Prognostic Indicator in Colorectal Adenocarcinoma

The purpose of this study was to investigate the association of CD8⁺ tumor-infiltrating lymphocytes (CD8⁺ TILs), microvascular density (MVD), and vascular endothelial growth factor (VEGF) with the TNM (Tumor-Node-Metastasis) stage, as well as to analyze their interrelationships in colorectal adenocarcinoma.

This cross-sectional study involved 50 FFPE samples of colorectal adenocarcinoma from the Laboratory of Anatomical Pathology at Dr. Soedarso Hospital. Microvascular density (MVD) was assessed on hematoxylin-eosin (H&E) slides, while CD8⁺ tumor-infiltrating lymphocytes (CD8⁺ TILs) and vascular endothelial growth factor (VEGF) expression were evaluated using immunohistochemistry (IHC). Correlation analysis was conducted between the biomarkers and the TNM stage, including its components depth of tumor invasion, lymph node status, and distant metastasis using the Chi-square test. Spearman's correlation was used to assess the relationships among CD8⁺ TILs, MVD, and VEGF.

High CD8⁺ TILs expression was significantly associated with negative lymph node status (p = 0.047; OR = 0.31, 95% CI = 0.098-1.001), absence of distant metastasis (p = 0.008; OR = 0.130, 95% CI = 0.025-0.680), and low TNM stage (p = 0.011; OR = 0.221, 95% CI = 0.067-0.727). The distribution of high MVD was correlated with deeper tumor invasion (p = 0.004; OR = 9.036, 95% CI = 1.741-46.890), positive lymph node status (p < 0.001; OR = 10.286, 95% CI = 2.768-38.215), and high TNM stage (p = 0.002; OR = 6.612, 95% CI = 1.924-22.728). High expression of VEGF showed a significant correlation with deeper tumor invasion (p = 0.036; OR = 0.675, 95% CI = 0.544-0.837). Spearman's test revealed a negative correlation between CD8⁺ TILs and MVD (r = -0.280, p = 0.049), and a positive correlation between MVD and VEGF (r = 0.303, p = 0.032).

High CD8⁺ TILs and low MVD are favorable prognostic factors in colorectal adenocarcinoma, whereas increased MVD and VEGF expression indicate tumor aggressiveness and enhanced angiogenesis. The combination of immune and angiogenic biomarkers with TNM staging could improve prognostic evaluation in colorectal adenocarcinoma.