Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Is there a clinical relevance of EMT in metastatic progression?- investigations of colorectal and breast cancer patient materials (#98)

Linda Bojmar 1 , Elin Karlsson 1 , Sander Ellegård 2 , Hans Olsson 3 , Marie Larsson 4 , Olof Hallböök 5 , Olle Stål 1 , Per Sandstrom 5
  1. Dept of Clinical and Experimental Research/Division of Surgery and Clinical Oncology, Linkoping University, Linkoping, Sweden
  2. Dept of Oncology, County Council of Ostergotland, Linköping, Sweden
  3. Dept of Pathology, County Council of Ostergotland, Linköping, Sweden
  4. Linkoping University, Linkoping, Swede, Sweden
  5. Dept of Surgery, County Council of Ostergotland, Linköping, Sweden

In vitro, the epithelial-mesenchymal transition (EMT) in relation to cancer is widely studied. However in vivo results, especially from human materials, are rare and lack clear proof.  Several microRNAs have been associated with EMT and metastasis. The microRNA 200 (mir-200) family is one of the most commonly reported, and acting negatively on ZEB, which is a repressor of CDH1 (E-cadherin) thereby supporting the epithelial maintenance. We aimed to investigate the role of microRNAs, especially mir-200, and associated EMT/metastasis markers in human breast (BC) and colorectal cancer (CRC) materials. Frozen and FFPE matched microdissected tissues from primary tumours and liver metastasis, and larger cohorts of colorectal liver metastases, and primary BC with more than 10 years of follow-up were used. Laser-capture microdissection (LCM), microRNA and mRNA extraction and expression analysis, microRNA in situ hybridization (ISH), immunohistochemistry, microRNA array profiling and primary cell culturing were performed. Correlations were found between the signalling pathway-members of the EMT process; both in primary tumours and metastatic lesions. Altered expression of EMT-players was associated with decreased survival from BC, and secondary recurrence in metastatic CRC in liver. Radiotherapy response, in terms of metastasis from BC, was significantly altered in relation to the expression of the mir-141/200c cluster. Correlations to many important factors in BC progression, eg. p53, ER and HER2 status and activation of the PI3K/AKT pathway could be possible explanations. ISH against the mir-200 confirmed selective expression to epithelial cells and microRNAs was shown to be more stable compared to mRNAs. LCM of CRC showed a significant decrease in mir-200 from normal mucosa to malignant cells, and when comparing metastatic CRC to non-metastatic. Correlations to FGF expression further strengthen that plasticity of cells is an important feature in the metastatic process and related factors could be useful prognostic and treatment predictive factors in metastatic cancers.