Comparison of Histopathology and Gene Expression Microarray Signatures of Spitzoid Tumors
Joseph D Hillman, Rong R Huang, Xinmin Li, Alistair J Cochran, Scott W Binder. David Geffen School of Medicine at UCLA, Los Angeles, CA
Background: Spitzoid tumors are often classified as Spitz nevus/tumor (S), atypical Spitz tumor (AS), or Spitzoid melanoma (SM) based on histopathologic appearance. We attempted to determine if gene expression microarray signatures (GAMS) derived from formalin-fixed, paraffin-embedded (FFPE) lesions diagnosed as S, AS, and SM correlate with histopathologic appearance.
Design: 15 FFPE samples, including 5 S, 5 AS, and 5 SM, were reviewed by 3 pathologists, cut into 8 µm sections, and dissected by LCM. Total mRNA was labeled with Nu-GEN WT-Ovation FFPE RNA Amplification System and FL-Ovation cDNA Biotin Module V2 kit, hybridized to the Affymetrix U133 Plus 2.0 Array. Differentially expressed genes were selected at a 1.5-fold expression difference and p<5.00E-2. Supervised clustering was performed with Partek Genomics Suite v.6.4, and unsupervised clustering was generated with dChip. Validation is in process.
Results: Unsupervised hierarchical cluster analysis failed to show clear clustering of AS, S and SM: the majority of samples (9 of 15) show no commonality of gene expression pattern correlated with their phenotype.
The supervised cluster was not able to yield unequivocally clear gene expression patterns for S, AS, and SM. 3 AS at the top of the cluster, 4 S just below, and SM at the bottom showed different gene expression profiles; however, 1 S fell into SM territory, and 2 AS clustered together with 2 S and 2 SM in the middle. Overall, SM tends to cluster together with a unique gene expression pattern apparently different from S and AS.
Conclusions: This study suggests that it may be possible to diagnose at least some SM as well as some lesions which would otherwise be diagnosed either S or AS as SM using a combination of histopathology and GAMS. Further study and clinical follow-up are necessary to confirm differences in gene expression and clinical behavior between SM and non-SM Spitzoid lesions.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 101, Wednesday Afternoon