Abstract

BACKGROUND: Although cyclin-dependent kinase 2 (CDK2) is known to be upregulated in certain cancers, its spatial expression pattern in melanocytic tumors has remained unknown. OBJECTIVE: To characterize CDK2 expression in benign and malignant melanocytic proliferations, including the gene expression profile of CDK2+ melanocytes. METHODS: We performed CDK2 immunohistochemistry (IHC) on normal skin and a tumor panel comprising over 200 nevi, in situ, invasive, and metastatic melanomas. We used spatial profiling to compare gene expression in CDK2+ and CDK2-negative melanocytes. RESULTS: Serial antibody dilutions revealed that CDK2 IHC reliably stains dermal-epidermal junction melanocytes in both lesional and non-lesional skin. Nevi progressively lose CDK2 expression with dermal depth (~88%), whereas the melanocytes of melanomas >0.8 mm retained strong CDK2 in their invasive aspects (~82%). PRAME (PReferentially expressed Antigen in MElanoma) and CDK2 expression are highly correlated in invasive and metastatic melanoma. Dual fluorescence IHC showed that increased CDK2 expression correlates with increased Ki67 positvity in melanocytes. CONCLUSION: CDK2 is expressed by malignant melanocytes in the deep dermis, suggesting a putative role during melanomagenesis. Deep dermal CDK2 positivity is highly specific and sensitive for invasive melanomas >0.8 mm. CDK2+ melanocytes have a comparatively increased cell proliferation index. Thus, CDK2+ IHC positivity may be a useful ancillary test for diagnosing challenging melanocytic tumors and, more generally, serve as a genetic proxy for melanocyte activation.

Financial Disclosure:
No current or relevant financial relationships exist.