Molecular prediction of metastasis in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent malignancy frequently occurring on body surfaces chronically exposed to ultraviolet radiation. While a large majority of tumors remain localized to the skin and immediate subcutaneous tissue and are cured with surgical excision, a small subset of patients with cSCC will develop metastatic disease. Risk stratification for cSCC is performed using clinical staging systems, but given a high mutational burden and advances in targeted and immunotherapy, there is growing interest in molecular predictors of high-risk disease.

Recent literature on the risk for metastasis in cSCC includes notable findings in genes involved in cell-cycle regulation, tumor suppression, tissue invasion and microenvironment, interactions with the host-immune system, and epigenetic regulation.

cSCC is a highly mutated tumor with complex carcinogenesis. Regulators of tumor growth and local invasion are numerous and increasingly well-understood but drivers of metastasis are less established. Areas of importance include central system regulators (NOTCH, miRNAs), proteins involved in tissue invasion (podoplanin, E-cadherin), and targets of existing and emerging therapeutics (PD-1, epidermal growth factor receptor). Given the complexity of cSCC carcinogenesis, the use of machine learning algorithms and computational genomics may provide ultimate insight and prospective studies are needed to verify clinical relevance.