Extracellular matrix proteins and chemoradiotherapy: α5β1 integrin as a predictive marker in rectal cancer

Aims: To investigate the effects of extracellular matrix (ECM) protein expression on the rates of apoptosis and proliferation in rectal cancers and subsequent response to chemoradiotherapy (CRT). Methods: The expression of fibronectin, collagen IV, laminin and the fibronectin receptor (FnR, α5β1 integrin) were analysed in 32 pre-treatment rectal cancer biopsies by immunohistochemistry. ECM expression was correlated with tumour mitotic index (MI), apoptotic index (AI) and histopathological response to CRT. Results: 18/32 cancers showed a poor response and 14/32 a good response (5/14 with complete pathological response) to CRT. Moderate to strong staining was seen in 22/32 cancers for fibronectin, 5/32 for collagen IV and 18/32 for laminin. Tumour FnR was related to stromal fibronectin content, and was significantly associated with CRT response; good responders having higher FnR expression compared to poor responders. No association was found between FnR expression and either MI or AI in pre-treatment biopsies, nor between MI or AI and CRT response. Conclusions: Tumour FnR expression is independent of MI and AI, and may serve as a useful marker for CRT response in rectal cancer.