Differential Gene Expression Profiles of Neurothekeomas, Nerve Sheath Myxomas, Cellular Fibrous Histiocytomas and Schwannomas by Microarray Analysis
S Sheth, X Li, SW Binder, SM Dry. UCLA, Los Angeles, CA
Background: Traditionally, neurothekeomas (NTK) and nerve sheath myxomas (NSM) were considered related cutaneous neoplasms of peripheral nerve sheath (PNS) origin based on light microscopic resemblances. Immunohistochemical and ultrastructural data indicate NSMs truly exhibit nerve sheath differentiation, while no such compelling evidence exists for NTKs. Although NTKs lack a specific immunohistochemical profile, similar antigen expression and histopathological patterns suggest NTKs may be categorized as fibrohistiocytic tumors (FHT). To date, no known studies have examined the histogenetic relationship of these tumors by utilizing molecular based techniques such as microarray-based gene expression profiles on formalin-fixed paraffin-embedded (FFPE) tissues.
Design: Cases of schwannomas (SCH), NSMs, mixed/cellular NTKs, and cellular FHTs diagnosed in the past 3 years were identified in our database. Archival FFPE tissue from 29 patients were selected for microarray analysis (7 SCH, 5 NSMs, 10 mixed/cellular NTKs, and 7 cellular FHTs). Following tumor RNA isolation, amplification, and labeling using commercially available kits, labeled targets were hybridized to the Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array. Acquisition of array images and data analyses were performed using appropriate software.
Results: Hierarchical clustering indicated discrete groups which correlated with histopathologically identified diagnoses. NSMs demonstrate very similar molecular genetic signatures to SCH, while NTKs, although distinct, more closely resemble FHTs.
|Histopathological Diagnoses||# Genes Upregulated (>3FC, p<0.01)||# Genes Downregulated (>3FC, p<0.01)|
|NTK vs NSM||73||289|
|NTK vs FHT||22||297|
|NTK vs SCH||258||578|
|NSM vs SCH||0||96|
|NSM vs FHT||179||336|