Tumor-Specific Diagnostic Marker for Transmissible Facial Tumors of Tasmanian Devils

Abstract

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.

Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process

“…Murchison and colleagues found that certain Schwann-cell markers are expressed across all tumors, but clearly other markers are variably expressed: NGFR (65%), nestin (45%), neuron-specific enolase (15%), and myelin basic protein by only 10% of tumors. Such patterns are evident for both primary and metastatic disease [2,9]. Similar, although less pronounced, observations can be made from an earlier study where 28% of DFTD cases expressed mel A [8].…”

“…Histologically, DFTD is an undifferentiated cancer, with tumor phenotype and cell of origin being the subjects of several studies. All available immunocytochemical data suggests a neural crest derivation [8], with more recent data supporting a Schwann cell origin [2,9]. If this is the case, then DFTD should be considered a malignant peripheral nerve sheath tumor (MPNST).…”

“…However, if one considers, broadly speaking, that CSCs are malignant cells with the ability to undergo self-renewal and the capacity to differentiate into a heterogeneous variety of cell types and produce multilineage cell progeny [4,5], then from available data it could be argued that both DFTD and CTVT represent such a process. Although not formally investigated for CSC attributes, both tumors have been the subject of extensive genetic/pathological analysis and xenograft studies [2,3,[6][7][8][9][10][11][12], and these provide some support for a stem cell element. In this article, analysis of existing data is presented, which may support the hypothesis that these unusual cancers represent models of the CSC process.…”

A second transmissible cancer in Tasmanian devils

“…2). Furthermore, tumors from RV and SN were negative for periaxin (PRX), an immunohistochemical marker that is diagnostic for DFT1 (12,17) (Fig. 2).…”

“…Standard hematoxylin and eosin (H&E) and immunohistochemical staining with a periaxin antibody (HPA001868; Sigma Aldrich) were performed on 3-μm paraffin sections from tumor tissues fixed in 10% neutral buffered formalin as previously described (17).…”