title: Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients.
abstract: BACKGROUND
  Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome.
  
  
  METHODS
  A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma" with those of the SqCC cells surrounded by "thin stroma."
  
  
  RESULTS
  The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033).
  
  
  CONCLUSIONS
  SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Taira
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Shinya
authors.initials: S
authors.lastname: Yanagi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nomori
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D018218:Neoplasms, Fibrous Tissue / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D005353:Fibronectins; C400567:LAMC2 protein, human; D007797:Laminin; D019859:Proto-Oncogene Proteins c-met; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7