[544] Stem Cell-Associated Markers Distinguish Melanoma from Malignant Peripheral Nerve Sheath Tumor

D Wagner, E Miller, Q Yang, G Scott, BP Rubin, J Huang. University of Nebraska Medical Center, Omaha, NE; University of Rochester Medical Center, Rochester, NY; Cleveland Clinic, Cleveland, OH; UCLA David Geffen School of Medicine, Los Angeles, CA

Background: Melanoma can have varied histologic appearances and often causes diagnostic confusion. When melanoma metastasizes to deep soft tissue or internal organs, a major differential diagnosis is with malignant peripheral nerve sheath tumor (MPNST) as both tumors may have spindle cell morphology and express S100 protein. The differential diagnosis becomes more difficult if additional melanoma markers such as melan A and HMB45 are equivocal. The cancer stem cell model states that a minority of cancer cells are cancer stem cells (CSC) with tumor initiation potential. However, melanoma is unique in that single unselected melanoma cells can initiate tumors in in-vivo models with high frequency, suggesting that melanoma cells have CSC properties. A previous study showed that stem cell-associated markers can differentiate melanoma from nevi. The current study was performed to determine if melanoma can be differentiated from MPNST with such markers.
Design: Two TMAs were used for the study, one containing 78 cases of melanoma and the other 68 cases of MPNST. The TMAs were stained with antibodies for EZH2 (VisionBio, 1:100), CD44 (eBioscience, 1:1000), SOX2 (R&D Systems, 1:100), C-Kit (Dako, 1:100) and Oct3/4 (BioCare, prediluted). Only tissue cores being at least 50% intact were scored.
Results: The results are summarized in Table 1. Among the stem cell-associated markers tested, SOX2 was expressed in 80% (55/69) of melanomas and 18% (12/66) of MPNSTs (p<0.001). C-Kit was expressed in 65% (50/76) of melanomas but none of the MPNSTs (p<0.001). Expression of other 3 markers was not statistically different between the two entities.

Table 1. Expression of stem cell-associated markers in melanoma and MPNST
Melanoma80% (55/69)87% (68/78)65% (50/76)100% (77/77)0% (0/78)
MPNST18% (12/66)56% (38/67)0% (0/48)94% (62/66)0% (0/67)

Conclusions: 1. Melanomas express stem cell-associated markers frequently, consistent with the laboratory observation that a single unselected melanoma cell can initiate tumor in in-vivo assays with high frequency. 2. A combination of SOX2 and C-Kit can differentiate melanoma from MPNST with high sensitivity and specificity.
Category: Dermatopathology

Monday, March 22, 2010 2:30 PM

Platform Session: Section F, Monday Afternoon


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