title: Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma.
abstract: The endothelin (ET) system influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of endothelin-1 (ET-1) is related to the angiogenic phenomenon in lung cancer and whether it could be involved in its clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1) and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial growth factor (VEGF) expression by a competitive-PCR approach to assess whether ET-1 expression was related to this angiogenic factor. A higher number of cases with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3% versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)). On the other hand, ETB mRNA was higher in normal lung tissues than in tumour samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm the presence of ET-1 protein and to determine its distribution and localisation. Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to be significant predictors of worse prognosis regarding both overall survival (P = 0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may represent a further indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.
authors.affiliation: Department of Surgery, University of Pisa, 56100 Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Silvia
authors.initials: S
authors.lastname: Gisfredi
authors.forename: Silvia
authors.initials: S
authors.lastname: Ursino
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Faviana
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Franca
authors.initials: F
authors.lastname: Melfi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D018572:Disease-Free Survival; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A