Overexpression of the alpha v beta 6 integrin in cervical squamous cell carcinoma is a prognostic factor for decreased survival

J Pathol. 2007 Jul;212(3):316-24. doi: 10.1002/path.2168.


Cervical squamous cell carcinomas are composed histologically of tumour cell islands surrounded by varying amounts of tumour stroma, the amount and composition of which are influenced by local TGF-beta(1). TGF-beta(1) is secreted in an inactive complex with latency-associated peptide (LAP). Both LAP and the extracellular matrix (ECM) protein fibronectin are important ligands for the integrin receptor alpha v beta 6. While alpha v beta 6 is only weakly expressed by normal epithelia, it is up-regulated in different carcinomas where it generally reflects a more aggressive phenotype. In cervical cancer, the expression of alpha v beta 6 has not thus far been investigated. Given the ability of alpha v beta 6 both to activate TGF-beta(1) and to interact with fibronectin, we studied correlations between the expression of these components and disease parameters in a large cohort of cervical cancer specimens. We analysed alpha v beta 6 expression using immunohistochemistry in primary cervical squamous carcinomas of FIGO stage IA to IIB patients and correlated the findings with formerly investigated fibronectin and TGF-beta(1) expression and clinico-pathological parameters. alpha v beta 6 expression was also examined in cervical intra-epithelial neoplasia (CIN) and lymph node metastases. alpha v beta 6 was only weakly expressed in normal epithelium but clearly up-regulated in CIN lesions. In carcinomas, strong expression of alpha v beta 6 in tumour cells correlated with different clinico-pathological parameters and with worse overall and disease-free survival. Furthermore, alpha v beta 6 expression correlated positively with TGF-beta(1) mRNA expression as well as with fibronectin expression. Overexpression of alpha v beta 6 in cervical squamous carcinomas is an unfavourable prognostic factor. This might reflect an increased capacity of alpha v beta 6-expressing tumour cells to migrate in a fibronectin-rich ECM and/or to activate TGF-beta(1) at the tumour/stroma interface, both of which processes may contribute to cervical cancer progression.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Carcinoma in Situ / chemistry
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cervix Uteri / chemistry
  • Cervix Uteri / pathology
  • Disease Progression
  • Female
  • Fibronectins / analysis
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization / methods
  • Integrins / analysis
  • Integrins / genetics*
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • RNA, Messenger / analysis
  • Survival Rate
  • Transforming Growth Factor beta / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Fibronectins
  • Integrins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • integrin alphavbeta6