Embryonic Stem Cell Markers Nestin and Sox2 Can Differentiate Metastatic Melanoma from Nodal Melanocytic Nevi and Serve as a Powerful Diagnostic Adjunct in Sentinel Lymph Node Evaluation and Melanoma Staging
Pei-Ling Chen, Wei-Shen Chen, Jianping Li, Anne C Lind, Dongsi Lu. Washington University School of Medicine, Saint Louis
Background: Sentinel lymph node (SLN) evaluation is a critical component of the pathologic staging of malignant melanoma (MM), and lymph node status provides one of the most powerful predictors of recurrence and survival. Using melanocytic markers on SLN enhances the sensitivity of melanoma detection. However, these stains have limited specificity in differentiating melanoma metastases from nodal nevus especially when the focus in question is small. It has been reported that 8% of lymphadenectomies harbor melanocytic nevi, and this percentage is higher in melanoma patients. Of the commonly used melanocytic markers, Melan-A and S-100 are indiscriminately expressed in melanoma and nevus cells, while S-100 highlights dendritic cells, making the interpretation of this marker in lymph nodes especially confusing. It has recently been shown that the embryonic stem cell marker Nestin is strongly expressed in MM and is associated with melanoma progression. Sox2, a key transcription factor in maintaining pluripotency of stem cells, binds the enhancer region of Nestin and is also expressed in MM. In this study, we sought to test the diagnostic utility of Nestin and Sox2 in differentiating metastatic melanoma (MetM) from nodal melanocytic nevi (nMN).
Design: A total of 39 specimens were retrieved from our archives: 21 lymph nodes (LNs) with MetM, 18 LNs with nMN from 18 patients (7 with history of melanoma). Immunostains were performed on FFPE tissue sections using Nestin and Sox2 antibodies.
Results: Of the 21 LNs with MetM, 16 showed diffuse 3+ Nestin, and 5 showed rare cells with 3+ Nestin. Nuclear Sox2 was expressed in 13 MetM and strongly highlighted rare cells in 3 cases. By contrast, none of the nMN expressed Sox2 (n=18), 13 nMN showed no Nestin, and 4 nMN showed rare cells with faint (<1+) Nestin. Of note, 1 case that was originally diagnosed as “subcapsular melanocytic rest” based on Melan-A staining and bland cytology showed rare cells with strong 3+ Nestin staining. Follow-up study revealed melanoma recurrence in the same LN region 2 years later.
Conclusions: We have shown that Nestin is strongly expressed in MetM (n=21; 100%), but not nodal nevi (n=17; 100%)(p<0.0001). Sox2 is also expressed in MetM (n=16; 76%) but not nodal nevi (n=18; 100%)(p<0.0001). This study provides evidence that embryonic stem cell markers Nestin and Sox2 can effectively differentiate nodal benign melanocytes from melanoma and serve as a powerful diagnostic adjunct in the staging of melanoma patients.
Monday, March 19, 2012 9:00 AM
Platform Session: Section F, Monday Morning