[537] 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.

Table 1
Histopathological Diagnoses# Genes Upregulated (>3FC, p<0.01)# Genes Downregulated (>3FC, p<0.01)
NTK vs NSM73289
NTK vs FHT22297
NTK vs SCH258578
NSM vs SCH096
NSM vs FHT179336
*FC=fold change




Conclusions: We are the first to report distinct gene expression profiles for NSMs and NTKs, which further substantiates the argument that these are separate entities. We offer molecular evidence suggesting NTKs may actually be a variant of FHTs rather than of PNS origin, unlike NSMs. Additional studies of NTKs and FHTs are planned to help determine if NTK is a distinct entity.
Category: Dermatopathology

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 73, Monday Morning

 

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