Polarização dos macrófagos e sua associação com fatores prognósticos em casos de neoplasias colorretais, considerando a presença e ausência de mutações nas metaloproteinases

Abstract

Background: Macrophages are a component present at the tumoral microenvironment. Given their plasticity, macrophages can either be seen as a neoplastic cell controlling factor or a tumor progression stimulating factor. Furthermore, macrophage polarization may hold prognostic value and manipulation of this condition could potentially be explored to control colorectal neoplasms. Objectives: Therefore, this work aimed to evaluate the M1 and M2 macrophage infiltration rates in colorectal neoplasia cases with presence and absence of metalloproteinase mutation, as well as investigate prognostic factors associated with the disease. Methods: In order to determine macrophage quantity and polarization, two sets of patients diagnosed with colorectal neoplasia were studied: (i) 33 patients with metalloproteinase mutation; and (ii) 33 patients without metalloproteinase mutation. Additionally, prognostic and survival factors associated with colorectal cancer were analyzed. Results: In terms of metalloproteinase mutation, 33 patients (54,1%) did not exhibit mutations, whereas 28 patients (45,9%) showed the referred mutation. When samples were grouped by tumoral stage, 10 were from patients in stage I (16,9%), 19 from stage II (34,2%), 25 from stage III (42,4%) and five from stage IV (8,5%). A total of 12 patient deaths (19,7%) were recorded during this study, seven of which were from the control group (21,2%) and five from the group with mutation (17,9%). The markers CD163 and CD206, indicative for M2 polarized macrophages, resulted in an average of 23 and 17, with a standard deviation of 21 and 17, respectively. On the other hand, the iNOS marker for M1 polarized macrophages returned a mean of five macrophages per site with a standard deviation of 11. Conclusion: The macrophage density observed through these markers did not demonstrate significant statistical differences between groupings with the variables employed in this study, including metalloproteinase mutation, age, gender, tumor region, tumor staging, TILS, tumor recurrence and clinical outcome. In the studied sample, no association was found between macrophage polarization and colorectal cancer prognostic variables, as well as survival. As for metalloproteinase mutation, a better survival rate was obtained for patients with the mutation. [resumo fornecido pelo autor]