Reviewing the genetic alterations in high‐risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets

Abstract

Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.

Specialized Antitumor Functions for Skin γδ T Cells

“…This body of work has clear relevance for potential treatment of human epithelial malignancies. SCC is the second most common malignancy (after basal cell carcinoma), affecting up to 1 million patients in the United States annually (31). Although most SCC lesions are successfully treated by surgical removal, metastasis to regional lymph nodes occurs in z5% of SCC patients and is associated with significant morbidity, demonstrating a need for additional treatment options.…”

Correlation of focal adhesion kinase expression with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma

“…Nevertheless, there are certain characteristics to a primary lesion that imply a higher risk of metastasis: primary lesion >2 cm in diameter; tumor thickness >6 mm; tumor on or around the ear; recurrent lesions; poorly differentiated grade; desmoplastic growth microvascular, lymphatic, or perineural invasion; advanced age; and a cSCC in an immunocompromised host . Even though the role of molecular factors in the lymphatic dissemination of cSCC has been studied; however, currently there are no clinically useful biomarkers of metastatic potential in primary cSCC . Coordinated regulation of the actin cytoskeleton is central to cell motility, invasion, and metastasis.…”

“…4,5 Even though the role of molecular factors in the lymphatic dissemination of cSCC has been studied; however, currently there are no clinically useful biomarkers of metastatic potential in primary cSCC. 6 Coordinated regulation of the actin cytoskeleton is central to cell motility, invasion, and metastasis. Focal adhesion kinase (FAK) and cortactin are two proteins known to play central roles in actin regulation and/or participate in tumor motility in other cancers.…”

Epidemiological and molecular features of cutaneous squamous cell carcinoma with perineural spread

“…8,80,81 In general, the initial genetic mutations triggered by UV exposure are followed by further driver gene mutations that lead to genomic instability and the loss of cell cycle control to result in tumourigenesis. 78,82,83 The tumour microenvironment may play a significant role in the pathogenesis and progression of disease yet this remains to be defined. 83…”

“…78,93 CDKN2A is involved in cell cycle regulation through retinoblastoma and p53 pathways and inactivating mutations or deletions in this gene may be involved in SCC tumourigenesis. 83 WNT/β-catenin signalling has been shown to be involved in BCC development, and a role in SCC tumourigenesis could also exist. 90 Gene expression arrays of cutaneous SCC samples have shown increased WNT ligands and receptor mRNA.…”