title: Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival.
abstract: We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define their usefulness as prognostic indicators of survival. A variable degree of specific staining in cancer cells was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically significant association between overexpression of TGF alpha, AR, and CRIPTO was observed. Enhanced expression of AR was significantly correlated with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of erbB-2 or erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpression significantly correlated with overall survival at univariate analysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results suggest that evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from post-surgical systemic therapies.
authors.affiliation: Dipartimento di Oncologia, Università di Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fontanini
authors.forename: M
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: S
authors.initials: S
authors.lastname: Vignati
authors.forename: S
authors.initials: S
authors.lastname: Chinè
authors.forename: M
authors.initials: M
authors.lastname: Lucchi
authors.forename: V
authors.initials: V
authors.lastname: Silvestri
authors.forename: A
authors.initials: A
authors.lastname: Mussi
authors.forename: S
authors.initials: S
authors.lastname: De Placido
authors.forename: G
authors.initials: G
authors.lastname: Tortora
authors.forename: A R
authors.initials: AR
authors.lastname: Bianco
authors.forename: W
authors.initials: W
authors.lastname: Gullick
authors.forename: C A
authors.initials: CA
authors.lastname: Angeletti
authors.forename: G
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: F
authors.initials: F
authors.lastname: Ciardiello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D066255:EGF Family of Proteins; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006133:Growth Substances / Q000032:analysis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D017978:Receptors, Growth Factor / Q000032:analysis*; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000032:analysis
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D017978:Receptors, Growth Factor; D016211:Transforming Growth Factor alpha