Gene and immunohistochemical expression of HIF‐1α, GLUT‐1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development

Abstract

ObjectiveTo analyze the gene and immunohistochemical expression of HIF‐1α, GLUT‐1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples.Material and MethodsThe gene expression was investigated by the real‐time PCR (qRT‐PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA.ResultsOur results showed that there was no statistically significant difference in HIF‐1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT‐1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA.ConclusionsIn summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT‐1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post‐translational regulatory mechanisms that act on the expression of these genes.

Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma

“…22,23 Additionally, adipophilin has been correlated with tumorigenesis in cells adapting to hypoxic conditions. 19 The expression of hypoxia-related proteins in AM and AC (Gal-3 and HIF-1α) has been reported, which may be interpreted as a response to hypoxic stress of these tumors and eventually may be found to represent a pathway for lipid droplet formation, as shown by the immunoexpression of perilipin 1 and adipophilin observed in this study. 3,24,25 The main limitations of this study are the size of the sample, especially of the AC group (which is a very rare tumor), and the lack of correlation of our results with clinical parameters, which were unavailable of complementary laboratory techniques to confirm and better illustrate our findings; therefore, further studies are needed on this topic.…”

“…In non‐cutaneous head and neck tumors, lipid droplets, as assessed by adipophilin immunohistochemical expression, have been reported mainly in salivary gland tumors such as mammary analog secretory carcinoma, carcinoma ex pleomorphic adenoma, and in high‐grade transformation adenoid cystic carcinoma. Finally, the authors of this previous study suggested that there is a relationship between upregulated lipogenesis and high‐grade transformation and that lipid droplets play roles in sustaining cell proliferation 2,18,19 . Additionally, because of their differentiation, sebaceous adenocarcinoma cells of the major salivary glands are consistently positive for adipophilin, which is a diagnostic tool for this disease 13,20,21 …”

“…Hypoxia mediated by either of the HIF1α and HIF2α isoforms promotes lipid droplet formation and accumulation in clear cell renal cell carcinoma (CCRCC) cells, and HIF1α induces the adipogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs), indicating that HIF control of fatty acid metabolism may be important for the tumorigenesis of CCRCC and that adipogenic differentiation of BMSCs may have a role in the cancer microenvironment 22,23 . Additionally, adipophilin has been correlated with tumorigenesis in cells adapting to hypoxic conditions 19 . The expression of hypoxia‐related proteins in AM and AC (Gal‐3 and HIF‐1α) has been reported, which may be interpreted as a response to hypoxic stress of these tumors and eventually may be found to represent a pathway for lipid droplet formation, as shown by the immunoexpression of perilipin 1 and adipophilin observed in this study 3,24,25 …”

“…Finally, the authors of this previous study suggested that there is a relationship between upregulated lipogenesis and high-grade transformation and that lipid droplets play roles in sustaining cell proliferation. 2,18,19 Additionally, because of their differentiation, sebaceous adenocarcinoma cells of the major salivary glands are consistently positive for adipophilin, which is a diagnostic tool for this disease. 13,20,21 In a previous study, we observed the coexpression of FASN and cyclooxygenase-2 (COX-2) in AM and AC.…”

Molecular and Cellular Modelling of Salivary Gland Tumors Open New Landscapes in Diagnosis and Treatment

“…Pleomorphic adenoma can transform into carcinoma (CXPA-Carcinoma ex pleomorphic adenoma) with an aggressive progression in 6% of cases [ 12 ]. This transition is accompanied by a switch in metabolic need of the growing mass, which abandons its dependency to glucose to adopt a long-lasting source of energy, such as fatty acids [ 18 ]. Benign tumors can be resected, but often reappear with a multifocal pattern.…”