Insights into the epithelial mesenchymal transition phenotype in cancer of unknown primary from a global microRNA...

We sought to study the microRNA regulation of epithelial mesenchymal transition (EMT), the acquisition of migratory, mesenchymal-like properties of epithelial cells, in cancer of unknown primary (CUP).

We studied the global expression profile of 982 microRNAs by means of microarray technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative.

EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level in the EMT-positive cases without, however, reaching statistical significance. MiR-205, a squamous tissue-specific marker, was very variable in the data set. Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR-200 family exhibited a trend of downregulation in EMT-positive cases. A similar pattern of miRNA expression was detected when the comparison took place between EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203, miR-205 and miR-200c were numerically downregulated in those tumours with high expression of the EMT marker N-cadherin.

The EMT-suppressive miR-203 and miR-200 family were consistently but non-significantly downregulated in CUP with the EMT phenotype. A larger study is warranted to further explore the role of microRNAs in CUP.