Establishment of Tissue Microarray for Molecular – Genetic Subclassification of Colorectal Cancer

Abstract

In 30-70% of colorectal cancers colonization of the liver leads to high mortality. Most liver metastases are unresectable and recurrence level after surgery is high (50%). Identification of patients at high risk to develop metastases would be a diagnostic tool of great importance and has the ability to pave the way for personalized medicine in colorectal cancer patients. MACC1 protein is recently identified as a new prognostic marker identifying tumours in colorectal cancer patients with the ability to develop metastases. Several transcriptional targets of MACC1 may lead to invasion of tumour cells and final metastatic colonization of distant organs. MACC1 expression is found to be high in tumour tissue of colorectal cancer patients, normal tissue shows moderate expression. Metastasised tumours reveal protein expression predominantly in the nuclei and non-metastasised tumours have mainly cytoplasmic MACC1 expression.

The aim of this study is to implement this knowledge in the clinic. With the help of tissue microarray technology prognostic ability of MACC1 was assessed in 90 colorectal cancer patients. Immunohistochemistry and immunofluorescence were performed in order to analyse expression and localisation of the protein. All samples were blinded for analysis and results evaluated independently. Development of tissue microarray technology as new method to asses protein expression profiles in colorectal cancers was successful. Different to previous findings MACC1 expression was found to be high in normal, tumour and metastasised tissue of patients who have metastases at time point of diagnosis. Further localisation of the protein was mainly cytoplasmic, at the same degree in metastasised and non-metastasised patients. Just those developing liver metastases show characteristic expression in the nuclei of tumour cells. Overall, analysis of MACC1 protein expression is not manageable in order to be integrated in routine diagnostics. Immunohistochemistry is not useful and analysis with immunofluorescence too complex for this purpose.