Immunoexpression of glucocorticoid receptor alpha (GRα) isoform and apoptotic proteins (Bcl‐2 and Bax) in actinic cheilitis and lower lip squamous cell carcinoma

• Published in: Journal of oral pathology & medicine 2018-09, Vol.47 (8), p.788-795
• Main Authors: Sena, Luana Samara Balduíno, Silveira, Éricka Janine Dantas, Batista, Aline Carvalho, Mendonça, Elismauro Francisco, Alves, Pollianna Muniz, Nonaka, Cassiano Francisco Weege
• Format: Article
• Language: English
• Subjects: actinic cheilitis; Active Transport, Cell Nucleus; Adult; Aged; Apoptosis; Bax; BAX protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Bcl‐2; Carcinogenesis; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cheilitis - etiology; Cheilitis - genetics; Cheilitis - pathology; Cytoplasm - metabolism; Disease Progression; Epithelial cells; Epithelial Cells - metabolism; Female; Gene Expression; glucocorticoid receptor; Glucocorticoids; Humans; Lip; Lip Neoplasms - etiology; Lip Neoplasms - genetics; Lip Neoplasms - pathology; Male; Malignancy; Metastases; Metastasis; Middle Aged; Nuclear transport; Protein Isoforms; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Squamous cell carcinoma
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12757

Background Actinic cheilitis (AC) is a potentially malignant disorder that can progress to squamous cell carcinoma (SCC), but this process is not fully understood. This study evaluated the immunoexpression of glucocorticoid receptor alpha (GRα) isoform and apoptotic proteins (Bcl‐2 and Bax) in AC and lower lip SCC (LLSCC). Methods Twenty‐two AC and 44 LLSCCs (22 with regional nodal metastasis and 22 without metastasis) were selected. The percentages of nuclear (GRα) and cytoplasmic (GRα, Bcl‐2, and Bax) staining in epithelial cells were assessed and correlated with clinical (tumor size/extent and clinical stage) and histopathological parameters (risk of malignant transformation for AC and histopathological grade of malignancy for LLSCCs). Results Expression of GRα was observed in all cases studied, with relatively high median percentages of positive staining. When compared to AC, LLSCCs exhibited lower nuclear expression and higher cytoplasmic expression of GRα (P < 0.05). Regarding clinicopathological parameters, significant differences were only found for cytoplasmic expression of GRα according to the histopathological grade of LLSCCs (P = 0.036). Higher expression of Bax compared to Bcl‐2 was observed in AC and LLSCCs (P < 0.05). In LLSCCs, there was a positive correlation between nuclear and cytoplasmic expressions of GRα (P = 0.006). Conclusion Reduced nuclear translocation and increased cytoplasmic expression of GRα may be important events in lip carcinogenesis but are not involved in the progression of LLSCC. The role of GRα in lip cancer development does not seem to be primarily related to modulations in the expression of Bcl‐2 or Bax.