The MicroRNA Profile of Granular Cell Tumours
MS Abi Daoud, N Zhang, H Feilotter, VA Tron. Queen's University, Kingston, ON, Canada
Background: Granular cell tumors were first described by Abrikossoff in 1926 as lesions derived from smooth muscle, and referred to as granular cell myoblastoma. However, the exact histogenesis of the tumor is debatable, with some evidence suggesting a neural cell of origin. The purpose of this study was to examine the microRNA (miRNA) expression profile of granular cell tumors when compared to normal skin and to determine if the histogenesis of granular cell tumors can be clarified with their miRNA profile. MicroRNAs are small non-coding RNAs that down regulate gene expression in cellular apoptosis, differentiation, development, and appear to be expressed in a cell lineage specific manner.
Design: To address our question, we began by comparing the miRNA expression profiles of granular cell tumors (n=8) to normal skin (n=2) using archival formalin fixed, paraffin embedded (FFPE) tissue and the Agilent miRNA microarray platform. Then, using Genespring software, we found both up-regulated and down-regulated miRNAs in the granular cell tumors relative to normal skin.
Results: Firstly, our results showed that unsupervised hierarchical clustering was able to separate the granular cell tumors from normal skin. The three most significantly down-regulated miRNAs were: miR-203, showing a 315-fold change (p ≤ 0.05), miR-200c, showing a 227-fold change (p ≤ 0.05), and miR-200b, showing a 116-fold change (p ≤ 0.05) in granular cell tumors when compared to their expression in normal skin. The three most significantly up-regulated miRNAs were: miR-370, showing a seven-fold change (p ≤ 0.05), miR-490-5p, showing a six-fold change (p ≤ 0.05), and miR-23a, showing a 5.6-fold change (p ≤ 0.05) in granular cell tumors when compared to their expression in normal skin.
Conclusions: The reduction of the miR-200 family has been previously shown to correlate with epithelial-mesenchymal transition (EMT) and thus with granular cell tumors, this finding is in line with its mesenchymal differentiation. We plan to compare the granular cell tumor profile with that of smooth muscle and neural tissue to better elucidate its lineage. In summary, this is the first description of the miRNA profile of granular cell tumors, and this work may lead to a better understanding of the histogenesis of this enigmatic tumor.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 58, Monday Morning