Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients

Yusuke Takahashi, Genichiro Ishii, Tetsuhiko Taira, Satoshi Fujii, Shinya Yanagi, Tomoyuki Hishida, Junji Yoshida, Mitsuyo Nishimura, Hiroaki Nomori, Kanji Nagai, Atsushi Ochiai

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


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). Conclusion: 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.

Original languageEnglish
Pages (from-to)1460-1467
Number of pages8
JournalJournal of Thoracic Oncology
Issue number9
Publication statusPublished - 2011 Sept
Externally publishedYes


  • Epithelial mesenchymal transition
  • Fibrous stroma
  • Prognostic indicator
  • Squamous cell carcinoma
  • Vascular invasion

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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