Use of fluorescent in-situ hybridisation in salivary gland cytology: A powerful diagnostic tool.

OBJECTIVE: Salivary gland cytology is challenging because it includes a diversity of lesions and a wide spectra of tumours. Recently, it has been reported that many types of salivary gland tumours have specific molecular diagnostic signatures that could be identified by fluorescent in-situ hybridisation (FISH). The aim of the present study was to demonstrate the feasibility and efficiency of FISH on routine cytological salivary gland smears. METHODS: FISH was conducted on 37 cytological salivary gland smears from 34 patients. According to the cytological diagnosis suspected, MECT1/MAML2 gene fusion and rearrangements of PLAG1, MYB, or ETV6 were analysed. The presence and percentages of cells that had gene rearrangements were evaluated. Results were compared with the histological surgical samples, available from 26 patients. RESULTS: The PLAG1 rearrangement was observed in 12/20 (60%) cases of pleomorphic adenoma. MECT1/MAML2 gene fusion was observed in 1:2 mucoepidermoid carcinomas but was not observed in five other tumours (two pleomorphic adenomas, one Warthin's tumour, one mammary analogue secretory carcinoma [MASC] and one cystic tumour). MYB rearrangement was observed in 4/4 adenoid cystic carcinomas. ETV6-gene splitting identified one MASC. CONCLUSION: Overall, FISH had a specificity of 100% and a sensitivity of 66.7%. When FISH and cytological analyses were combined, the overall sensitivity was increased to 93.3%. It can thus be concluded that when the FISH analysis is positive, the extent of surgery could be determined with confidence pre-operatively without needing a diagnosis from a frozen section.

The profibrotic cytokine transforming growth factor-ß1 increases endothelial progenitor cell angiogenic properties.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-ß1 modulation of EPC angiogenic properties. METHODS: TGF-ß1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-ß1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-ß1 in ECFCs by using short interfering RNA. RESULTS: Total TGF-ß1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-ß1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-ß1 receptors. CONCLUSIONS: TGF-ß1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-ß1 may play a role during vascular remodeling in fibrotic disease states via EPCs.