Análise da imunoexpressão de CXCL12 e CXCR4 em carcinomas de células escamosas de língua oral em indivíduos jovens e idosos

Abstract

Oral tongue squamous cell carcinoma (OTSCC) is an epithelial malignant neoplasm characterized by the potential for invasion and development of lymph node metastases. Although usually diagnosed in individuals over 60 years of age in the last two decades, a significant increase in the incidence of OTSCC has been observed in patients under 45 old of age. Scientific evidence suggests the existence of differences in the profile of the genetic alterations of OTSCC among young and elderly individuals, in addition to possible differences in the biological behavior of this neoplasm related to age. Studies have shown that the chemokine CXCL12, also called stromal cell-derived factor 1α (SDF-1α), and the chemokine receptor CXCR4 may be involved in the pathogenesis and progression of OTSCC. However, to date, little is known about possible differences in the expression of these proteins in the OTSCC related to the age of the patients. Thus, this study aimed to evaluate the immunoexpression of CXCL12 and CXCR4 in OTSCC in young and elderly individuals. The sample consisted of 42 cases of OTSCC (21 of them diagnosed in young individuals [≤45 years] and 21 in the elderly [≥ 60 years old]). Clinical data (sex, age, anatomical location of the lesion and clinical stage) were collected from medical records. In the morphological study, the histopathological grade of malignancy of the OTSCC was evaluated on the front of tumor invasion. For the immunohistochemical study, the percentages of epithelial cells with nuclear (CXCR4) and cytoplasmic (CXCR4 and CXCL12) positivity were established in 10 microscopic magnification of the tumor invasion front. CXCL12 positivity was observed in 10 (47.6%) cases of OTSCC in the group of young individuals and in 12 (57.1%) cases in the elderly group. The isolated analysis of the positive cases for CXCL12 revealed a median percentage of 35.7% in the young group and 2.4% in the elderly group, with no statistically significant difference between the age groups (p = 0.222). Cytoplasmic positivity for CXCR4 was found in 16 (76.2%) cases of OTSCC in the group of elderly individuals (median: 23.9%) and in 11 (52.4%) cases in the group of young individuals (median: 1, 1%) (p = 0.052). In turn, the analysis of CXCR4 nuclear immunoexpression revealed positivity in 17 (80.9%) cases of OTSCC in the elderly group (median: 10.6%) and in 8 (38.1%) cases in the (median: 0.0%), with a statistically significant difference between groups (p = 0.001). Considering the clinicopathological parameters, statistically significant differences were observed only in the immunoexpression of CXCL12 in the OTSCC of elderly individuals. In this group, lesions with invasion pattern in small groups of neoplastic cells revealed greater cytoplasmic immunoexpression of CXCL12 (p = 0.027). A positive statistically significant correlation was found only for the cytoplasmic and nuclear expression of CXCR4 in the OTSCC, both for the elderly group (r = 0.507, p = 0.019) and for the young group (r = 0.495, p = 0.023). The results of the present study suggest a potential involvement of CXCR4 and CXCL12 in the pathogenesis of some cases of OTSCC and, in addition, support the existence of differences in the molecular bases of this malignant neoplasia related to the patients' age. Tumor progression in OTSCC, however, may not be related to the expression of these proteins.