Immunohistochemical expression of integrins and extracellular matrix proteins in non-small cell lung cancer: correlation with lymph node metastasis

Lung Cancer. 2003 Jul;41(1):65-70. doi: 10.1016/s0169-5002(03)00146-6.


Purpose: For patients with non-small cell lung cancer (NSCLC), the biggest threat to survival is metastasis. During metastatic cascade, tumor cells interact with extracellular matrix (ECM) through certain adhesion molecules such as integrins. The aim of this study was to analyze the distribution of the main integrins and ECM in a series of patients with NSCLC to assess their distribution and correlate with lymph node (LN) metastasis of NSCLC.

Methods: Formalin-fixed and paraffin-embedded tissues of NSCLC with (n=45) or without (n=23) regional LN metastasis were obtained form 68 surgically treated patients. The expression of fibronectin, collagen type IV, tenascin and the integrin subunits (alpha2, alpha3, alpha4, alpha5 and beta1) was studied by immunohistochemistry. Chi-square and Fisher's exact tests were used to compare groups and parameters.

Results: Extensive (>50% of section area) fibronectin and collagen type IV staining were seen in 22 and 55% of tumors, respectively, with focal areas of immunoreactivity seen in another 75 and 38% of tumors, respectively. Tenascin staining showed just focal areas of immunoreactivity in 21% of tumors. Interstitial collagen matrices were more frequently lost in LN metastasis (P=0.007). Integrins alpha2, alpha5 and beta1 expressions were present in 9, 12 and 26% of tumors, respectively. The expression of integrins alpha5 and beta1 was significantly associated with LN metastasis (P=0.04 and 0.005, respectively).

Conclusions: Increased expression of integrins alpha5 and beta1, and lost expression of collagen matrices significantly correlated with LN metastasis of NSCLC. These findings suggested that enhanced expression of integrins and disrupted collagen stroma in NSCLC might promote tumor cell survival and invasiveness.

MeSH terms

  • Adenocarcinoma / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism
  • Collagen Type IV / blood
  • Extracellular Matrix Proteins / biosynthesis*
  • Fibronectins / blood
  • Humans
  • Immunoenzyme Techniques
  • Integrins / biosynthesis*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Tenascin / blood


  • Collagen Type IV
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrins
  • Tenascin