title: Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-β1.
abstract: BACKGROUND
  Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with fibrous stromal invasion are newly introduced subtypes of small lung adenocarcinoma. AIS is a small localized adenocarcinoma in which growth is restricted to neoplastic cells along preexisting alveolar structures without fibrous stromal invasion. In MIA, by contrast, tumor cells have infiltrated the myofibroblastic stroma. Transforming growth factor (TGF)-β is known to be produced by progressor tumors, and excessive TGF-β contributes to a pathological excess of tissue fibrosis. TGF-β1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-β1 expression and clinicopathological microinvasion in patients with small lung adenocarcinoma.
  
  
  METHODS
  The study participants were 45 patients who underwent curative surgery for AIS and MIA 3 cm or less in size. Those tumors were assessed based on immunohistochemical staining using anti-TGF-β1 antibody. The TGF-β1 status was assessed immunohistochemically using the Allred 8-unit system.
  
  
  RESULTS
  The rates of TGF-β1 positivity in the AIS and MIA groups were 27.3% and 65.2%, respectively (P <0.05). The median of Allred score was 0.5 (range 0-5) in the AIS group and 3.0 (range 0-6) in the MIA group (P = 0.0017).
  
  
  CONCLUSIONS
  We suggest that TGF-β1 expression is likely to be significantly stronger in patients with MIA than in those with AIS, and the increased expression may be associated with minimal invasion and infiltration of the myofibroblastic stroma.
authors.affiliation: Department of Chest, Breast and Endocrine Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan. i-karo@mui.biglobe.ne.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
authors.forename: Akiteru
authors.initials: A
authors.lastname: Goto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nanjo
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kudo
authors.forename: Shinogu
authors.initials: S
authors.lastname: Takashima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaharada
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Kurihara
authors.forename: Kimito
authors.initials: K
authors.lastname: Orino
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ogawa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D061206:Neoplasm Micrometastasis; D009367:Neoplasm Staging; D011379:Prognosis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D053773:Transforming Growth Factor beta1