Using global gene expression to discriminate thin melanomas with poor outcomes

Abstract

Most melanomas present as thin lesions (1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasized to regional lymph nodes or distant sites compared with those that followed the typical course with good response to wide local excision alone. Patients who were disease-free for a minimum of 10 y served as controls (n D 10) to the experimental group who developed metastasis (n D 9). Laser capture microdissection was used to specifically isolate cancer cells from formalin-fixed paraffin-embedded tissue with subsequent gene expression analysis on Affymetrix Human Transcriptome Array 2.0 Arrays. Although gene expression differences were observed between the patients with thin melanoma with poor clinical outcome and those with good clinical outcome, neither the number of genes nor the magnitude of the fold difference was very substantial or significant. Cluster analysis with this subset of genes could definitively separate a subset of the poor responders from the good responders, but there remained a mixed group of tumors that could not be predicted from gene expression alone. Pathway analysis identified cellular processes that were regulated based on the response, including categories commonly associated with melanoma progression. Ultimately, we concluded that there were very few differences between these groups. Future research will be required and investigation of the mutational landscape may be another strategy to uncover genomic changes that drive recurrence and metastasis in thin melanoma.

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas

“…These results suggest a molecular heterogeneity in the metastatic process in relation to thickness and may indicate that different molecular mechanisms could mediate disease progression and metastasis development in thin compared to thick melanomas. To date, only few studies have investigated the molecular processes underlying thin melanoma pathogenesis and no molecular predictor of disease progression has been identified (30,(33)(34)(35). Overall, our results add evidence supporting the hypothesis that thin melanoma cannot be considered just an early stage of melanoma progression but, at least in some cases, a different type of tumor (33).…”

Metastases risk in thin cutaneous melanoma: prognostic value of clinical-pathologic characteristics and mutation profile

“…However, existing prognostic factors cannot reliably differentiate high- and low-risk TM patients. To the best of our knowledge, only a few studies have analyzed the molecular profile of TM and to date there is no molecular predictor of disease progression [ 12 , 13 ]. In recent years, significant advances in the genetic field have led to the identification of specific driver mutations in melanocytic tumors [ 14 – 16 ].…”