[79] 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.

Table 1: miRNA Relative Expression in MPNST and DM
Probep-valueRelative Fold Expression Change in DM vs. MPNST
hsa-miR-138-1/20.0190-9.61
hsa-miR-4520.0441-3.98
hsa-miR-44300.01312.09



Conclusions: Our preliminary data show, for the first time, that miR-138 is a very promising probe candidate for differentiating MPNST from DM (>9.5 folds expression difference). Although recent studies have suggested a role for miR-138 disregulation in melanoma development, the significance of miR-138 in the pathogenesis of MPNST is unclear and needs further analysis. The other miRNAs (miR-452 and miR-4430) may also be of potential significance. We intend to expand our case selection further and confirm our results using real-time PCR. We believe that miRNA expression analysis, specifically miR-138, can help differentiate and elucidate potential therapeutic targets for MPNST and DM.
Category: Bone & Soft Tissue

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 10, Monday Morning

 

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