title: Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis.
abstract: To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase-2 (MMP-2) in 11/50 patients (22%), membrane-type 1 matrix metalloproteinase (MT1-MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP-2 in 32/33 patients (97%). In CF areas, both CD34-positive (blood and lymphatic) vessels and D2-40-positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease-free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.
authors.affiliation: Hospital Pathology Center, Hirosaki University School of Medicine, Hirosaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okudera
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamata
authors.forename: Shingo
authors.initials: S
authors.lastname: Takanashi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Takao
authors.initials: T
authors.lastname: Tsushima
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ogura
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000098:blood supply / Q000150:complications* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000098:blood supply / Q000150:complications* / Q000473:pathology; D042583:Lymphangiogenesis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011658:Pulmonary Fibrosis / Q000150:complications*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D020778:Matrix Metalloproteinase 2