[499] Stem Cell-Associated Markers Are Useful in Distinguishing Melanoma from Nevi
D Wagner, G Scott, Q Yang, J Huang. University of Rochester Medical Center, Rochester, NY; UCLA School of Medicine, Los Angeles, CA
Background: Distinguishing melanoma from nevi can be difficult in certain cases. A previously published study showed that stem cell marker EZH2 is frequently expressed in melanoma but very rarely in nevi. Since EZH2 is a polycomb gene involved in controlling cell proliferation, this finding suggests possible molecular pathway in melanoma as well as providing a useful tool in the differential diagnosis of difficult cases. We studied additional stem cell-associated markers as well as EZH2 in a large cohort of melanoma and nevi.
Design: Two tissue microarrays (TMA) were constructed consisting of 80 cases of primary melanoma, 74 cases of metastatic melanoma and 76 cases of nevi. Sections were stained with antibodies for: Bmi-1 (Upstate, 1:100), EZH2 (VisionBio, 1:100), CD44 (eBioScience, 1:1000), SOX2 (R&DSystems, 1:100) and OCT3/4 (BioCare, prediluted). Only intact cores were scored.
Results: Among the stem cell associated markers studied, SOX2 and EZH2 were frequently overexpressed in primary and metastatic melanomas in comparison to nevi (p<0.001). The other three markers showed no difference among the groups. The results are summarized in Table 1.
Expression of stem cell-associated markers in melanoma, metastatic melanoma and nevi (positive/total (%positive)) | Oct3/4 | Bmi1 | SOX2 | EZH2 | CD44 | | Melanoma | 0/78 (0%) | 0/80 (0%) | 55/69 (80%) | 68/78 (87%) | 77/77 (100%) | | Metastatic Melanoma | 0/73 (0%) | 0/74 (0%) | 42/73 (57%) | 67/70 (96%) | 70/70 (100%) | | Nevi | 0/77 (0%) | 0/76 (0%) | 13/72 (18%) | 9/69 (13%) | 72/72 (100%) |
Conclusions: In addition to EZH2, we have identified another stem-cell associated marker SOX2 which is frequently overexpressed in primary and metastatic melanomas but infrequently in nevi. SOX2 is a transcription factor involved in the regulation of embryonic development and in the determination of cell fate which is essential to maintain self-renewal of undifferentiated embryonic stem cells. It will be important to determine if EZH2 and SOX2 function in the same pathway or different pathways to regulate melanoma cell growth. A combination of both markers provide high sensitivity and specificity in the differential dioagnosis of melanoma from nevi. Bmi1, CD44 and Oct3/4 are not differentialy expressed in the two lesions.
Category: Dermatopathology
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 82, Monday Morning
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