Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer

Five-year survival rates in colorectal cancer (CRC) vary dramatically from ∼93% in patients with localised stage I tumours to ∼6% in patients with metastasised inoperable disease (Siegel et al, 2012). The decision to administer adjuvant chemotherapy in CRC is predominantly stage-dependent. All stage III and high-risk stage II patients are recommended to receive adjuvant treatment. In contrast, patients with stage I and low-risk II disease generally do not receive adjuvant chemotherapy after resection of the primary tumour, as 5-year survival rates are high and there is only minimal benefit in unselected patients (O'Connell et al, 2004; Edge and Compton, 2010). Recently, gene expression profiling has been used to identify high-risk stage II patients who can possibly benefit from adjuvant chemotherapy. Two published gene signatures have proven to be able to select stage II cancer patients for adjuvant treatment: the Oncotype DX Colon Cancer Assay (12 genes) and the ColoPrint (18 genes). Both signatures seem to perform better than most conventional risk factors (Salazar et al, 2010; Webber et al, 2010; Kelley et al, 2011) and are currently being further validated. The discovery of novel biomarkers for predicting tumour behaviour is not only valuable from a prognostic viewpoint, but can also help to gain insight into the mechanisms that cause disease progression and metastasis formation. Differences in tumour cell survival, migration, invasion and extracellular matrix remodelling are all likely to have a role (Hanahan and Weinberg, 2000). To turn a locally invasive colorectal tumour into a metastasising one very few, if any, additional genetic changes are required (Jones et al, 2008). It is possible that the factors driving initial metastasis formation from the primary tumour also promote tumour recurrence at later stages of the disease, following surgical removal of liver metastases (Eberhard et al, 2012). After resection of colorectal liver metastases, the vast majority of patients experience tumour recurrence within 2 years. However, the patients that remain disease-free beyond 2 years have a good chance of 5-year survival without additional therapy (Nordlinger et al, 1996; Fong et al, 1999; Simmonds et al, 2006; de Jong et al, 2009). This is most likely due to favourable tumour characteristics. The rationale of this study was to obtain further insight into the mechanisms causing tumour progression and metastases formation. Gene expression profiling and proteomics were used to detect differences between stage IV CRC patients that recur within 6 months after resection vs those that fail to recur for >2 years. Subsequently, we analysed whether expression of the identified factors also predicts metastasis formation in early stages of CRC.