title: Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.
abstract: Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan. ytogashi@kuhp.kyoto-u.ac.jp
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Masago
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubo
authors.forename: Daichi
authors.initials: D
authors.lastname: Fujimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sakamori
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagai
authors.forename: Young Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Kaori
authors.initials: K
authors.lastname: Togashi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects / Q000235:genetics