title: Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer.
abstract: Angiogenesis is a recently described prognostic factor in non-small-cell lung cancer. Platelet-derived endothelial cell growth factor (PD-ECGF), shown to be the enzyme thymidine phosphorylase (TP), induces angiogenesis in vitro and in vivo. High intracellular levels of the enzyme are associated with increased chemosensitivity to pyrimidine antimetabolites. PD-ECGF/TP expression was evaluated immunohistochemically in surgically resected specimens from 107 patients with operable non-small-cell lung cancer using the P-GF,44C monoclonal antibody. High expression of PD-ECGF/TP was found in 25% of cases and was associated with high vascular grade (P = 0.01). Fourteen of 32 (44%) high vascular grade tumours showed a positive reactivity for PD-ECGF/TP vs 13/75 (17%) of low/medium vascular grade. Positive expression was observed more frequently in T2-staged cases than in T1 (P = 0.04). While overall survival was not affected (P = 0.09), subset analysis revealed that node-negative patients with positive PD-ECGF/TP expression had a worse prognosis (P = 0.04). The results suggest that PD-ECGF/TP may be an important molecule involved in angiogenesis in non-small-cell lung cancer. Up-regulation of the enzyme defines a more aggressive tumour phenotype in patients with node-negative disease. Assessment of vascular grade and PD-ECGF/TP expression should be taken into account in the design of randomized trials assessing the role of adjuvant chemotherapy in non-small-cell lung cancer.
authors.affiliation: Department of Radiotherapy and Oncology, University Hospital of Iraklion, Crete, Greece.
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: M
authors.initials: M
authors.lastname: Comley
authors.forename: R M
authors.initials: RM
authors.lastname: Whitehouse
authors.forename: D C
authors.initials: DC
authors.lastname: Talbot
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D015588:Observer Variation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor