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))
|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.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 82, Monday Morning