Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares

Abstract

Cystic adenoid carcinoma (ACC) is a malignant tumor of epithelial origin, with an unpredictable clinical course and its pathogenesis is not well understood. The interaction of the CXCL12 (SDF-1) chemokine with its CXCR4 (CD184) receptor induces, through several pathways, important intracellular signaling in neoplastic pathogenesis, regulating events such as proliferation, differentiation, apoptosis, chemotaxis and metastasis. The CXCL12/CXCR4 complex has been associated with several events associated with malignant tumor progression in humans, but little is known about its role in malignant salivary gland neoplasm. The objective of this study was to analyze the immunohistochemical expression of CXCL12 / CXCR4 in cystic adenoid carcinomas of the salivary glands, related to histopathological parameters, aiming to obtain information about the role of such proteins in the pathogenesis, biological behavior and prognosis of this neoplasm. Through the immunocytochemistry, the intratumoral, peritumoral and antibody positive indexes were investigated against CXCL12 and CXCR4 and analyzed in relation to histomorphological parameters characterized by the WHO histopathological classification system and the system of histopathological grading of malignancy proposed by van Weert et al in 17 CAC. Were evaluated 17 ACCs with predominance of the tubular histopathological pattern and cases of high histopathological grade of malignancy. There was a trend towards higher expression of CXCL12 in the intratumoral region of the cribriform pattern and in the peritumoral region of the solid pattern. The general IP of expression of CXCL12 was similar in histopathological patterns. A statistically significant difference was observed for the intratumoral expression of CXCL12 (p = 0.005) and general index of expression (p = 0.009). There was a significant association of the intratumoral expression of CXCL12 in relation to the degree of malignancy, especially in low grade cases (p = 0.005). The general index expression of CXCL12 was significantly associated with the histopathological grade of malignancy (p = 0.009). There was a tendency for greater expression of CXCR4 in the intratumoral and peritumoral region of the tubular pattern. The general index of expression of CXCR4 tended to decrease in solid, cribriform and tubular patterns. There was no significant association of intratumoral, peritumoral and general expression of CXCR4 in relation to the histopathological grade of malignancy of the sample. There was no statistically significant correlation between the expression of CXCL12 and CXCR4 in the tumor regions evaluated in both the low and high histological grade of malignancy. It was concluded that the immunoexpression of CXCL12 and CXCR4 in salivary glandular cystic adenoid carcinoma is practically equivalent in the intratumoral and peritumoral regions. However, considering the histological subtypes of CAC evaluated here, there was a trend towards greater immunoexpression of the chemokine in the intratumoral region, suggesting some role of this chemokine in the regulation of the mechanisms that guarantees the proliferation and maintenance of neoplastic cell viability when interacting with the CXCR4 receptor that was strongly expressed in all tumor regions. In addition, this receptor would also be, in turn, making the neoplastic cells apt to invade and / or metastasize.