Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities

Abstract

Melanoma is characterised by its ability to metastasise at early stages of tumour development. Current clinico-pathologic staging based on the American Joint Committee on Cancer criteria is used to guide surveillance and management in early-stage disease, but its ability to predict clinical outcome has limitations. Herein we review the genomics of melanoma subtypes including cutaneous, acral, uveal and mucosal, with a focus on the prognostic and predictive significance of key molecular aberrations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords: 31-gene expression profile; acral; biomarkers; cutaneous; desmoplastic; driver genes; melanoma; mucosal; mutations; predictive; prognostic; uveal.

Figure 1

Histopathology of melanoma subtypes. (A) CM of superficial spreading type features an in situ component within the epidermis with underlying dermal invasion. (B) Desmoplastic melanoma, a type of CM, is comprised of a dermal proliferation of atypical spindled cells associated with lymphoid aggregates. (C) Acral melanoma often shows a lentiginous (linear) in situ growth pattern along the epidermal ridges with underlying invasion into the dermis. (D) Mucosal melanoma arises in non‐keratinising wet mucosa, shown here invading the subepithelial stroma of respiratory type mucosa in the nasal sinuses. (E) Uveal melanoma preferentially metastasises to the liver as pictured here with accompanying immunohistochemistry showing (F) staining for SOX10 in the melanoma cells, (G) loss of BAP1 staining in the melanoma cells with retention of normal staining in hepatocytes and lymphocytes, and (H) no staining for BRAF VE1, indicating the absence of a BRAF V600E mutation.

Figure 2

Molecular representation of the mutations associated with the RAS/RAF/MEK/ERK pathways in melanoma, including the MITF signalling cascade. GPCR, G‐protein coupled receptor; RTK, receptor tyrosine kinase. *KIT amplifications are seen in ∼10% of CMs, ∼9.5% of AMs, ∼15% MMs 64. ^†Cyclin D1 is also amplified in ∼18% of CMs 65. ^‡MDM2 is also amplified in ∼6% of CMs 66. Adapted from 67.