title: Pulmonary emphysema and tumor microenvironment in primary lung cancer.
abstract: BACKGROUND
  To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer.
  
  
  METHODS
  The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD).
  
  
  RESULTS
  Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05).
  
  
  CONCLUSIONS
  The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis.
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Murakami
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: kaueda@c-able.ne.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Fumiho
authors.initials: F
authors.lastname: Sano
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masataro
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Nishimoto
authors.affiliation: Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011656:Pulmonary Emphysema / Q000150:complications* / Q000000981:diagnostic imaging; D012189:Retrospective Studies; D017154:Stromal Cells / Q000201:enzymology; D014057:Tomography, X-Ray Computed; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Extracellular matrix; Lung cancer; Matrix metalloproteinases; Microenvironment; Pulmonary emphysema