Differential Expression of miR-138 in Malignant Peripheral Nerve Sheath Tumors and Desmoplastic Melanomas
Shaozhou K Tian, Patrick Koty, Omar Sangueza, Julia S Gouffon, Shadi Qasem. Wake Forest School of Medicine, Winston-Salem, NC; Affymetrix, Santa Clara, CA
Background: Differentiating malignant peripheral nerve sheath tumors (MPNST) from desmoplastic melanomas (DM) can be a diagnostic challenge due to overlapping morphology and immunophenotype. Treatment regimens and prognosis vary greatly depending on the cancer type. The aim of this study was to identify similarities and differences between these two categories of tumors and potentially find a molecular signature unique to either tumor type as a method of differentiation. MicroRNAs (miRNA) are regulatory molecules that act by means of mRNA inhibition. With practicality and reproducibility in mind, we performed miRNA expression analysis on archived formalin-fixed paraffin-embedded tissue.
Design: A pilot group of 5 MPNST and 3 DM cases with sufficient tissue for miRNA expression analysis was selected. Each case was independently confirmed by a soft tissue pathologist and a dermatopathologist and correlated with follow-up. Blocks containing at least 80% tumor were selected for macrodissection and subsequent total RNA extraction. Samples were quality checked on a Nanodrop for quantity (>1 mg total per 8 uL) and acceptable 260/280 ratio (1.8-2.0). Universal miRNA expression was analyzed with the GeneChip miRNA 3.0 Array (Affymetrix Inc). Raw data was imported into Partek Genomics Suite 6.6 and analyzed using parametric t-test assuming equal variance.
Results: Significant probe sets were identified based on a p-value <0.05 and a significant difference of +/- 2 fold-change between the two groups. Candidate miRNAs showing the most significant differences included miR-138-1/2 (p-value 0.019), miR-452 (p-value 0.044), and miR-4430 (p-value 0.013). See table 1.
|Probe||p-value||Relative Fold Expression Change in DM vs. MPNST|