The increased PDGF-A, PDGF-B and FGF-2 expression in recurrence of salivary gland pleomorphic adenoma.

BACKGROUND: Pleomorphic adenoma (PA) is the most common salivary gland tumour. Although classified as benign, it has a tendency to recur (recurrent pleomorphic adenomas (RPA)), as well as the ability to undergo malignant transformation. It has been suggested that mutations in various families of growth factors and growth factor receptions are involved in the autonomous growth of tumour cells. The aim of the present study was to investigate the participation of platelet-derived growth factor (PDGF)-A, PDGF-B, PDGF-Rα, fibroblast growth factor (FGF)-2, Flg and BEK in PA, RPA and recurrent pleomorphic adenoma with malignant transformation (TRPA). METHODS: 18 cases of PA, 16 cases of RPA and two cases of RPA with focal malignant transformation (TRPA) were analysed for growth factor expression utilising immunohistochemical techniques via tissue microarray. RESULTS: There was a significant difference in PDGF-A, PDGF-B, PDGF-Rα, FGF-2, Flg and BEK expression in all groups. When comparing non-recurrent with recurrent tumours, PDGF-A, PDGF-B, PDGF-Rα, FGF-2, Flg and BEK reactivity in RPA was stronger than that observed in PA. All proteins were highly expressed in TRPA. CONCLUSIONS: This research suggests that PDGF-A, PDGF-B, PDGF-Rα, FGF-2, BEK and Flg can be related to the recurrence of PA. In addition, this study shows that TRPA cells overexpress all growth factors, which has been reported in association with the malignant transformation.

FGF-2, TGFbeta-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study.

UNLABELLED: Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. OBJECTIVES: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor beta-1 (TGFbeta-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFbetaR-II and PDGFR-alpha) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. MATERIAL AND METHODS: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. RESULTS: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-alpha had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFbeta-1 and TGFbetaR-II were negative in all samples. CONCLUSIONS: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of these cells through the FGFR-1.

Study of growth factors and receptors in carcinoma ex pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.