Associação entre a via dos receptores TOLL símile com a via dos fatores de necrose tumoral nas lesões pré-invasoras e câncer de colo uterino

Abstract

Introduction: Cervical cancer is an important cause of death in women worldwide. The persistent infection of human papillomavirus (HPV) is recognized as one of the causative agents. The persistence of HPV infection is necessary, but insufficient to the development of cervical cancer. HPV may alter the host´s immune response in order to escape from the immune attack and use it favoring the malignant transformation. The TOLL Like receptors (TLR) are membrane receptors present in the defense cells and they are responsible to recognize pathogens structures and activate signaling pathways leading to an activation of innate immune response .In humans, 10 different types of TOLL Like receptors are recognized. Previous studies had shown association between TLR expression and cervical cancer. Tumor necrosis factors (TNF-, TNF-) are one of the main mediators of skin and mucosa inflammation .They have a potent antiproliferative effect on normal epithelial cells. Numerous observations indicate that TNF may influence the fate of HPV infected cells. Deregulated TNF expression within the tumor microenvironment appears to favor malignant cell tissue invasion, migration, and ultimately metastasis formation .The TLR and TNF are play crucial role in the development of the cervical cancer. Still, to date, there are no studies about a possible association between them in the cervical cancer. This study showed the association between the expression of TLR and TNF in cervical cancer, HPV related lesions when compared to normal controls. Results: It was observed an association between expression levels of TLR2 with TNF- (p=0.01) and with TNF- (p=0.021) in cervical cancer and CIN groups. The expression of TLR4 was also associated with the expression of TNF- (p=0.016) and TNF- (p=0.025) in the groups. Differently, TLR3 was not statistically associated with 11 TNF nor TNF . It was also found, in accordance with previous studies, that there are higher levels of expression of TLR2 (p=0.032), TLR4 (p<0.001), TNF- (p=0.007) e TNF- (p=0.036) in the CIN and cervical cancer groups when compared to normal control. Once again, it was not observed statistical differences between TLR 3 among the three groups. Conclusion: There might be an association between TOLL like receptors 2 and 4 pathways with the imunogical response of tumor necrosis factors and . Those markers are also expressed in higher levels in cervical cancer and pre malignant lesions when compared to normal controls. The TOLL like receptor 3 was not associated with tumor necrosis factors. There were no differences between the level of expression among cervical cancer, CIN and controls groups