Exploring macrophage polarization as a prognostic indicator for colorectal cancer: Unveiling the impact of metalloproteinase mutations.

Background: Macrophages play a crucial role in the tumor microenvironment, displaying remarkable plasticity that allows them to either suppress or promote tumor progression. Their polarization into M1 or M2 phenotypes could have significant prognostic implications, and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.

Aim: To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia, specifically comparing cases with and without metalloproteinase mutations. Additionally, it sought to explore potential prognostic factors associated with the disease.

Methods: The study involved two cohorts of patients diagnosed with colorectal neoplasia: 33 patients with metalloproteinase mutations and 33 without. Macrophage quantity and polarization were assessed using markers indicative of M1 (iNOS) and M2 (CD163, CD206) macrophages. Prognostic factors and survival outcomes related to colorectal cancer (CRC) were also analyzed.

Results: Among the 61 patients, 28 (45.9%) exhibited metalloproteinase mutations, while 33 (54.1%) did not. Tumor staging revealed that 16.9% were in stage I, 34.2% in stage II, 42.4% in stage III, and 8.5% in stage IV. The study recorded 12 patient deaths (19.7%), with 21.2% from the control group and 17.9% from the mutation group. M2 macrophages, identified by CD163 and CD206 markers, had mean counts of 23 and 17, respectively, with standard deviations of 21 and 17. In contrast, M1 macrophages, identified by iNOS, had a mean count of five per site, with a standard deviation of 11.

Conclusion: The study found no statistically significant differences in macrophage density between groups, irrespective of metalloproteinase mutation status, age, gender, tumor region, staging, TILS, tumor recurrence, or clinical outcomes. No association was observed between macrophage polarization and CRC prognosis or survival. However, patients with metalloproteinase mutations demonstrated a better survival rate, suggesting a potential protective role of this mutation in colorectal neoplasia.