Έκφραση πρωτεϊνών θερμικού σοκ και νεοαγγειογένεση στα νεοπλάσματα των σιελογόνων αδένων

Abstract

IntroductionSalivary gland neoplasms comprise a wide group of tumors with diverse histology and broad biologic behavior, often presenting difficulties in their definitive diagnosis and treatment. In the last decades, the prominent role of angiogenesis in the neoplastic process has been recognized, and alterations of its promoters and inhibitors have been investigated in most human tumors. However, angiogenesis in salivary gland neoplasms has not been thoroughly studied.Material and MethodsWe evaluated the immunohistochemical expression of various angiogenesis-related molecules and the vascularity of 61 malignant (16 adenoid cystic carcinomas, 12 mucoepidermoid carcinomas, 11 polymorphous low grade adenocarcinomas, 9 adenocarcinomas NOS, 6 salivary duct carcinomas, 3 carcinomas ex-pleomorphic adenomas, 2 lymphoepithelial carcinomas, 1 myoepithelial carninoma, 1 clear cell carinoma NOS) and 18 benign salivary gland neoplasms (13 pleomorphic adenomas, 5 Warthin tumours).The evaluated molecules were: angiogenesis-promoter vascular endothelial growth factor (VEGF). angiogenesis-inhibitor Endostatin. angiogenesis related molecule collagen angiogenesis related molecule HSP47. endothelial marker FVIIIR:Ag. Vascularity was assessed by calculation of MicroVessel Density (MVD) and by FVIIIR:Ag immunostaining intensity.ResultsVEGF was expressed in 83.6% of malignant and 94.44% of benign neoplasms. Endostatin was expressed in 91.8% and 100% of malignant and benign cases respectively. Collagen XVIII was expressed in 100% of both benign and malignant neoplasms. HSP47 was expressed in 78.68% of malignant and 100% of benign neoplasms.All markers predominantly showed a diffuse pattern of immunostaining (more than 50% positive cells). VEGF immunostaining intensity varied widely among cases, ranging from weak to strong for both malignant and benign cases. Endostatin, Collagen XVIII and HSP47 presented varying immunointensity for malignant cases, whereas benign cases mainly presented strong immunostaining.Statistical analysis correlated VEGF expression in malignant neoplasms with TNM stage and extraparenchymal infiltration (p=0,0005 and 0,00063 respectively). The total score of immunoreactivity for Endostatin, Collagen XVIII and HSP47 was significantly higher in benign compared to malignant cases (p=0.01, p=0.02, and p=0,00996 respectively). Furthermore, HSP47 positivity and intensity was statistically higher in benign neoplasms, compared to malignant (p=0,0067 and p=0.0249 respectively). Additionally Endostatin immunoexpression correlated with Collagen XVIII expression in benign cases (p<0.001). No association was found regarding tumor MVD. However, immunostaining intensity of the endothelial marker FVIIIR:Ag was higher in malignant tumours (p=0,013).ConclusionsOur results show that benign compared to malignant salivary gland neoplasms express higher levels of Endostatin, Collagen XVIII and HSP47. Ιn malignant neoplasms an increase in the ratio of angiogenic to angiostatic elements is observed. It suggested that enhanced angiogenesis may contribute to salivary gland carcinogenesis.