title: Clinical significance of epidermal growth factor receptor mutations and insulin-like growth factor 1 and its binding protein 3 in advanced non-squamous non-small cell lung cancer.
abstract: This study of patients with advanced non-squamous non-small cell lung cancer (NSCLC) evaluated epidermal growth factor receptor (EGFR) mutation status and two serum markers, serum insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3), for their associations to response to gefitinib therapy and for their prognostic impact. An immunoradiometric assay determined levels of IGF1 and IGFBP3 in serum from 68 patients with advanced non-squamous NSCLC. The peptic nucleic acid locked nucleic acid clamp method determined their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. Having IGF1-positive serum as determined by the 75th percentile and having wild-type EGFR were both independent negative predictive factors for geftinib treatment by multivariate logistic regression model analysis. Both having serum positive for IGF1 as determined by the 25th percentile and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. We demonstrated that having IGF1-positive serum predicts a negative response to gefitinib therapy independent of EGFR mutational status. We also demonstrated that both IGF1-positive serum and wild-type EGFR were independent poor prognostic factors in patients with non-squamous NSCLC who received gefitinib therapy.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507 Japan. masago@kuhp.kyoto-u.ac.jp
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Masago
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.forename: Young Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Hatachi
authors.forename: Akiko
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagai
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irisa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sakamori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mio
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011799:Quinazolines; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D000077156:Gefitinib