Z Gastroenterol 2014; 52 - KG164
DOI: 10.1055/s-0034-1386186

Epithelial-mesenchymal transition-associated microRNA expression pattern in human biliary tract cancer: a clinical and pathological approach

R Illig 1, T Kiesslich 2, 3, R Kemmerling 1, B Alinger 1, E Klieser 1, F Berr 4, D Neureiter 1
  • 1Institute of Pathology, Paracelsus Medical University, Salzburg, Austria
  • 2Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria
  • 3Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria
  • 4Paracelsus Medizinische Privatuniversität, Universitätsklinik für Innere Medizin I, Salzburg, Austria

Introduction: Epithelial-mesenchymal-transition (EMT) is a key mechanism in tumor progression and metastasis which is regulated among others via microRNA-200 (miRNA) family members.

Aim: Referring to this, we investigated six miRNAs and their expression pattern in cancer of the biliary tract (BTC) to evaluate their possible role in tumor progression and (de-) differentiation.

Methods: Total RNA was isolated from FFPE blocks (n = 34) obtained from surgically resected BTC patients between 1997 and 2013 using the miRNeasy FFPE isolation kit (Qiagen®). Expression levels of six miR-200 family members (miRNA-141, -205, -429, -200a, -200b, -200c) were measured by quantitative RT-PCR followed by statistical analyses to investigate possible correlation between miRNA expression and clinical-pathological data. Additionally, tissue microarrays of these BTCs were characterized for proliferation (p16, p27, p53 and Ki-67) and differentiation markers (Vimentin, Cytokeratin-7 and -19) by immunohistochemistry.

Results: Overall, we observed a collinear expression pattern of all six miRNAs in BTC tumor specimen's independent from tumor grade or stage. Interestingly, once lymph node or other metastatic dissemination occurred, all miRNAs were significantly down-regulated in these advanced tumor stages, suggesting a threshold of miRNA expression levels and tumor spread. Additionally, tumor specimen with high Vimentin protein expression pattern (indicating mesenchymal differentiation) revealed a significant association with reduced miRNA expression regarding tumor region analysis.

Conclusion: We observed a highly coordinated and tumor stage-dependent as well as Vimentin-associated expression pattern of six miRNAs in BTC specimens. Their changes of expression in advanced tumor stages may indicate their possible key regulatory role in preventing tumor progression (EMT). Thus, finding the triggers for their down-regulation would provide possible clinical targets for early diagnosis of progression and therapy, respectively.