Diagnostic Value of Neural Progenitor Cell Markers Nestin and Sox2 in Melan-A Negative and HMB-45 Negative Melanoma
Pei-Ling Chen, Wei-Shen Chen, Jianping Li, Anne C Lind, Dongsi Lu. Washington University School of Medicine, Saint Louis
Background: Malignant melanoma (MM) accounts for less than 5% of skin cancers but ∼80% of skin cancer death. Histologically, MM exhibits a wide range of cytologic and architectural features that mimic a variety of tumors, making the diagnosis of MM one of the most challenging tasks in surgical pathology. Established immunomarkers of melanocytic differentiation, including Melan-A and HMB45, have been widely used to differentiate MM from its mimickers. Unfortunately, it is well-documented that melanoma can lose these differentiation markers at various phases of growth. HMB45 is lost in up to 50% of metastatic melanoma (MetM), and progressive loss of Melan-A is also observed from stage I to stage IV MM. Furthermore, in the broader category of spindle cell melanoma (SCM), including the rare S-100+ desmoplastic melanoma (DM), the sensitivity of HMB45 and Melan-A is at best 22%, further limiting the utility of these two markers. It has recently been shown that the neural progenitor cell markers Nestin and Sox2 are expressed in MM. In the present study, we sought to test the utility of Nestin and Sox2 in Melan-A/HMB45 negative melanomas, including MetM, DM and the broader category of SCM.
Design: A total of 33 melanoma specimens were retrieved from our archives: 12 MetM, 7 pure DM, 7 mixed SCM/DM, and 7 SCM. Of the 12 MetM, 10 showed complete loss of Melan-A staining, 8 complete loss of HMB45, and the remaining cases showed only focal Melan-A or HMB45 staining. Six of the MetM (50%) were metastatic melanomas of unknown primary site. Immunohistochemical studies were performed on FFPE tissue sections using anti-Nestin and Sox2 antibodies.
Results: Of the 21 DM and SCM, cytoplasmic Nestin was strongly positive in 20 cases (95%). Nuclear Sox2 was also detected in 17 cases (81%). Of the 12 cases of MelanA-/HMB45- MetM, Nestin was strongly and diffusely positive in 10 cases (83%) and patchy in 2 cases (17%). Sox2 was strongly positive in 9 cases (75%) and negative in 2 cases (17%).
Conclusions: In this study, we have shown that despite the loss of established melanocyte-specific markers in MetM, expression of neural stem cell markers Nestin and Sox2 persists. This immunophenotype suggests that some melanomas may adopt a more progenitor-cell like state with disease progression. Diagnosing MetM that do not express the established differentiation melanocytic markers is particularly challenging to practicing pathologists. Our results provide evidence that Nestin and Sox2 can be powerful adjuncts in diagnosing Melan-A/HMB45 negative, neural progenitor-cell like MetM, as well as DM/SCM.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 120, Wednesday Afternoon