Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas

Abstract

Sentinel lymph node evaluation is a critical component of melanoma staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. One of the well-known diagnostic pitfalls in melanoma sentinel lymph node evaluation is the presence of nodal melanocytic nevi, which has been demonstrated in up to 26% of lymphadenectomy specimens and specifically in melanoma patients. Melanocytic markers enhance the sensitivity of melanoma detection in sentinel lymph nodes. However, established markers such as anti-melan-A/MART1, S100 protein and SOX10 antibodies cannot discriminate melanoma metastasis from nodal nevi. Recent studies have demonstrated strong expression of neural stem/progenitor cell markers nestin and SOX2 in melanoma. In this study, we tested the diagnostic utility of nestin and SOX2 in differentiating metastatic melanomas from nodal nevi. Twenty-three lymph nodes with metastatic melanomas and 17 with nodal nevi were examined. Of the 23 metastatic melanomas, 18 showed diffuse and strong (3 þ ) nestin, 4 showed rare cells with strong (3 þ ) nestin, and one showed diffuse but faint (1 þ ) nestin staining. Nuclear SOX2 was positive in 13 metastatic melanomas. In contrast, 15 nodal nevi showed no nestin, and 2 showed rare cells with very faint (o1 þ ) nestin staining. SOX2 was negative in 13 nodal nevi. Overall, nestin was strongly expressed in metastatic melanomas (n ¼ 22/23; 96%), but not in nodal melanocytic nevi (n ¼ 15/17; 88%; Po0.0001). SOX2 was also expressed in metastatic melanomas (n ¼ 13/23; 57%) but not in the majority of nodal melanocytic nevi (n ¼ 13/16; 81%; P ¼ 0.02). In one lymph node harboring metastatic melan-A-negative desmoplastic melanoma, nestin and SOX2 strongly highlighted the infiltrating tumor cells, suggesting the potential clinical value of these two markers in desmoplastic melanoma lymph node biopsies. This study provides evidence that nestin and SOX2 can effectively differentiate nodal melanocytic nevi from metastatic melanomas and serve as powerful diagnostic adjuncts in melanoma staging. Modern Pathology (2013) 26, 44-53; doi:10.1038/modpathol.2012; published online 17 August 2012Keywords: metastatic melanomas; nestin; nodal melanocytic nevi; SOX2 Malignant melanoma is a malignant tumor of melanocytes that accounts for less than 10% of all skin cancer diagnoses but the majority of skin cancerrelated deaths. 1 For patients diagnosed with malignant melanoma, sentinel lymph node biopsy is an essential component of tumor staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. [2][3][4] When melanoma metastasizes, a regional lymph node is the most common site, and tumor burden can range from rare tumor cells to complete effacement of lymph nodes. The presence of either micro-or macrometastasis in a single lymph node changes melanoma staging from stage I to stage III. 5 In addition, a single positive lymph node signifies a decrease in 10-year survival from 95% (stage IA) to 68% (stage II...

TGF‐β induces SOX2 expression in a time‐dependent manner in human melanoma cells

“…Recent studies have highlighted the significance of SOX2 in melanoma progression. In particular, research has found SOX2 to influence melanoma cell invasion (Girouard et al., ) and to be coexpressed with nestin in patient samples (Chen et al., ; Laga et al., ). Moreover, SOX2 expression in melanoma patient samples was found to correlate with increased tumor thickness (Laga et al., ), which suggests a potential role for SOX2 in the clinic.…”

Clinicopathological analysis of basal cell carcinoma of the anal region and its distinction from basaloid squamous cell carcinoma

“…The staining was strongest in the basal cell layer and progressively decreased with maturing epithelium. Although SOX2 is not considered to 40 Our findings indicate that unlike its potential role as a cancer stem-like cell/ tumor-initiating cell marker in various cancers such as lung adenocarcinoma, 41 gastric carcinoma, 42 breast carcinoma, 43 head and neck squamous cell carcinomas, 44 and metastatic melanomas, 45 it does not appear to mediate regulation of progenitor cells of the folliculo-sebaceous unit or interfollicular epidermis from which basal cell carcinomas originate. 29 The differential expression of SOX2 not only allows for a reliable distinction between basal cell carcinomas and basaloid squamous cell carcinomas but also provides opportunities for selective therapeutic intervention in basaloid squamous cell carcinomas.…”

Prognostic significance of nestin in primary malignant melanoma of the oral cavity

“…Moreover, Chen et al [17] reported that nestin is expressed in vascular endothelial cells; thus, lymph node blood vessels served as internal positive controls. In our study, nestin expression was observable in endothelial cells in all melanoma cases.…”