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Abstract 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‐β 1 . TGF‐β 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 αvβ6. While αvβ6 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 αvβ6 has not thus far been investigated. Given the ability of αvβ6 both to activate TGF‐β 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 αvβ6 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‐β 1 expression and clinico‐pathological parameters. αvβ6 expression was also examined in cervical intra‐epithelial neoplasia (CIN) and lymph node metastases. αvβ6 was only weakly expressed in normal epithelium but clearly up‐regulated in CIN lesions. In carcinomas, strong expression of αvβ6 in tumour cells correlated with different clinico‐pathological parameters and with worse overall and disease‐free survival. Furthermore, αvβ6 expression correlated positively with TGF‐β 1 mRNA expression as well as with fibronectin expression. Overexpression of αvβ6 in cervical squamous carcinomas is an unfavourable prognostic factor. This might reflect an increased capacity of αvβ6‐expressing tumour cells to migrate in a fibronectin‐rich ECM and/or to activate TGF‐β 1 at the tumour/stroma interface, both of which processes may contribute to cervical cancer progression. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Hazelbag et al. (Mon,) studied this question.