Remodelling of Extracellular Matrix in Rectal Cancer and Preoperative Radiotherapy

BACKGROUND Preoperative radiotherapy reduces local recurrence due to rectal cancer, but increases postoperative morbidity. The aim of this thesis was to study the impact of radiotherapy on extracellular matrix (ECM) remodelling enzymes and growth factors after radiotherapy and also their possible use as surrogate markers for complications. A secondary aim was to explore the use of these enzymes and growth factors as markers for tumour classification and risk predictors of metastases and death of rectal cancer. MATERIALS AND METHODS In paper I-III 91-110 patients undergoing surgery with or without preoperative radiotherapy were studied through biopsies taken from tumour tissue and adjacent mucosa as well as plasma samples during surgery. Clinical parameters were registered and the patients were followed yearly. Paper IV encompasses 32 patients with sequential biopsies before treatment and from the surgical specimen. Twenty of them received preoperative radiotherapy. Protein levels of matrix metalloproteinase (MMP)-1, -2, -9 (Papers I and IV), urokinase plasminogen activator (uPA) (Papers III-IV), plasminogen activator inhibitor-1 (PAI-1) (Papers III-IV), transforming growth factor-β1 (TGF-β1) (Papers II and IV), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) (Paper IV) and calprotectin (Paper IV) were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed (Paper IV) for tissue-type plasminogen activator (tPA). The localisation of calprotectin in mucosa was determined by immunohistochemistry (Paper IV).