Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Correlations between biomarkers for invasion/metastasis and patient clinical outcomes in rectal cancer (#60)

Seong Beom Ahn 1 , Charles Chan 2 , Sun Young Kwun 2 , Betty Pai Chun Lin 2 , Owen F. Dent 3 , Pierre H. Chapuis 3 , Mark S. Baker 1
  1. Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
  2. Anatomical Pathology, Concord Hospital , University of Sydney, Sydney, NSW, Australia
  3. Colorectal Surgery, Concord Hospital, University of Sydney, Sydney, NSW, Australia
Colon and rectal cancer (CRC) is one of most common malignancies by incidence and cause of death. Five-year survival rates are dramatically lower in stage C (metastasised to lymph nodes) than in stage B (non-metastasized). In other words, tumour metastasis is directly responsible for the majority of cancer deaths. Therefore it is important to understand the relationship between biomarkers of invasion/metastasis and patient clinical outcomes (e.g., recurrence and 5-year survival) to minimise metastasis-related deaths. Urokinase plasminogen activator receptor (uPAR) plays a number of critical roles in cancer metastasis and is overexpressed in many cancers including CRC. The Integrin β6 subunit is an epithelial cell-surface restricted integrin and is also significantly overexpressed in CRC. These data suggest that both uPAR and integrin β6 may be specific, sensitive metastasis-related protein biomarkers in CRC. Furthermore, there is considerable evidence (i.e., cross-over IPs, proximity ligation assays and peptide arrays) that these two cell-surface proteins can interact with each other.

In this study, ~396 stage B and C resected rectal cancer specimens with paired normal tissues were examined for expression levels of uPAR, integrin β6 and the uPAR. β6 complex. The expression levels of antigens were correlated with various clinico-pathological outcomes including 5-year overall survival. In addition, we utilised two differentially discriminatory epitope specific MAbs; the first (MAb R4) identifying a uPAR epitope expressed on stromal associated cells (e.g., macrophages and fibroblasts) and the second (MAb ADI#3936) identifying uPAR expression levels on CRC epithelial cells. Given the considerable discussion in the research community regarding where uPAR is actually expressed in human CRC, we examined correlations of uPAR expression with patient outcomes using both MAbs in both locations.