Análise da imunoexpressão da isoforma alfa do receptor de glicocorticoide e de proteínas da apoptose (BCL-2 e BAX) em queilites actínicas e carcinomas de células escamosas de lábio inferior

Abstract

Actinic cheilitis (AC) is a potentially malignant disorder caused by ultraviolet (UV) radiation. The transformation of this lesion into a squamous cell carcinoma (SCC) can be observed in up to 20% of cases, but the molecular events involved in this process are not yet fully understood. In the development and progression of malignant neoplasms, investigations have highlighted the role of the glucocorticoid receptor (GR). Through the modulation of several processes, with emphasis on apoptosis, the high expression of the GRα isoform (GRα) has been associated with less aggressive biological behavior indicators in neoplasms. Despite this evidence and the possible use of corticosteroids in the treatment of ACs, little is known about the expression of GRα in these lesions and on a possible participation in the development of lower lip SCCs. Thus, this study aimed to evaluate the expression of GRα and proteins involved in apoptosis (BCL-2 and BAX) in cases of AC, with varied risks of malignant transformation, and of lower lip SCC. The sample consisted of 22 cases of AC and 44 cases of SCC (22 with regional nodal metastasis and 22 without regional nodal metastasis). Clinical data (sex and age of patients, tumor size, regional metastasis, distant metastasis and clinical stage) were collected from biopsy request forms and medical records. In the morphological study, the ACs were classified according to the risk of malignant transformation (KUJAN et al., 2006; WARNAKULASURIYA et al., 2008) and the histopathological grade of malignancy of the SCC was evaluated on the tumor invasion front (BRYNE et al., 1992). For the immunohistochemical study, under 400× magnification, the percentages of epithelial cells with nuclear (GRα) and cytoplasmic (GRα, BCL-2 and BAX) were established in 5 microscopic fields of the epithelial lining of the ACs and in 10 fields of the SCC invasion front. All cases of AC and SCC revealed expression of GRα, both in nucleus and cytoplasm, with high percentages of immunopositivity. Compared to the SCCs, the ACs showed a lower percentage of cytoplasmic positivity (p < 0.05) and a higher percentage of nuclear expression for GRα (p < 0.05). The ACs also exhibited, compared to SCCs, lower percentages of BAX positive cells (p < 0.001) and higher BCL-2 expression (p < 0.001). No significant differences were identified in the expression of GRα (cytoplasm and nucleus), BCL-2 and BAX in relation to the presence or absence of regional metastasis in SCCs (p > 0.05). Considering the clinicopathological parameters of the lesions, there was a significant difference only for the cytoplasmic expression of the GRα in relation to the histopathological grade of malignancy of the SCC (p = 0.036), characterized by the tendency to higher positivity in the lesions with a high grade when compared to the low grade lesions. Significantly higher positivity percentages for BAX in relation to BCL-2 were found, both for ACs and SCCs, regardless of the clinicopathological characteristics of the lesions (p < 0.05). There was a weak positive correlation, statistically significant, only for the cytoplasmic and nuclear expressions of the GRα in the SCCs (r = 0.406; p = 0.006). The results of the present study suggest an important role for GRα in lip carcinogenesis, which does not appear to be primarily related to the modulation of the expression of BCL-2 and BAX proteins. Tumor progression in lower lip SCCs, however, may not be related to GRα expression.