Differential Stathmin 1 Immunoreactivity in Spitz Nevi and Melanoma
Jocelyn Moore, Elizabeth Hyjek, Thomas Krausz. University of Chicago Medicine, Chicago, IL
Background: The distinction between benign Spitz nevi and malignant melanoma (MM) can at times be difficult or impossible based on morphology and immunohistochemical analysis. Stathmin 1 plays a role in cell cycle regulation via microtubule dynamics and has increased expression in several human malignancies. Both cyclin D1 and stathmin 1 are thought to be subject to regulation by MiRNA-193b, which is down regulated in MM and is associated with increased expression of CCND1 in melanomas as compared to benign nevi. Another recent publication establishes increased stathmin 1 expression in MM as compared to benign nevi and suggests that stathmin 1 is a potential oncogene in melanoma. Overexpression of cyclin D1 in Spitz nevi compared to melanomas via IHC has been reported; however; there are currently no publications investigating stathmin 1 expression in Spitz nevi. This study compares immunoreactivity of cyclin D1 and stathmin1 antibodies in melanomas, conventional nevi and Spitz nevi.
Design: Specimens were selected on the basis of morphological diagnosis from the pathology archive. Twenty MM (12 superficial spreading, 5 nodular, 1 spindle cell, 1 lentigo maligna and 1 metastasis), 10 conventional nevi (5 compound and 5 intradermal), and 5 Spitz nevi were stained with antibodies to stathmin 1 (Cell Signaling 3352 1:50) and cyclin D1 (ThermoFisher SP4 1:30) using established IHC protocols. The melanocytic cells were analyzed for staining pattern and intensity. For stathmin 1, diffuse cytoplasmic staining was considered a positive result. For cyclin D1, reactivity was quantified as follows: <10% of melanocyte nuclei stained = weak, 10-50% = moderate, and >50% = strong expression.
Results: Diffuse cytoplasmic staining for stathmin 1 was present in 19 of 20 MM cases (95%). One nodular MM specimen showed very weak diffuse cytoplasmic staining. Nine of 10 (90%) conventional nevi and 5/5 (100%) Spitz nevi were negative. One intradermal nevus showed weak diffuse staining for stathmin 1. Cyclin D1 was strongly positive in all MM and Spitz nevi, but showed variable reactivity in conventional nevi. Two nevi showed weak expression, 5 nevi showed moderate reactivity, and 3 showed focally strong expression.
Conclusions: In this study, cyclin D1 staining was variable in conventional nevi, but strongly positive in both MM and Spitz nevi, limiting its usefulness as a discriminatory marker in this setting. Our preliminary findings suggest that stathmin 1 antibody may be a useful supportive marker in differentiating Spitz nevi from MM in morphologically difficult cases; this needs to be validated on a larger number of cases.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 67, Monday Morning