Revisiting determinants of prognosis in cutaneous melanoma

Abstract

The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma. Cancer 2015;121:4108–4123. © 2015 American Cancer Society.

Underexpression of Specific Interferon Genes Is Associated with Poor Prognosis of Melanoma

“…Several mRNA expression profiling datasets have been produced to study melanoma prognosis [10, 23, 27, 33, 35–40]. We used the TCGA2STAT package to download gene expression data from The Cancer Genome Atlas (TCGA) repository [41].…”

“…Therefore, it is critical to identify patients who are not at a significant risk of metastasis and death due to the disease. The predictive power of clinical factors is limited [3, 5, 6] (e.g., staging based on the tumor size and the number of metastatic sentinel lymph nodes [7]), therefore clinicians are seeking more accurate molecular markers to improve risk models and to avoid unnecessary treatment of low-risk patients [8–10]. …”

“…Gene expression profile signatures have useful information on the molecular status of cells and they can predict the prognosis of many cancers [11–14], including melanoma [10, 15–18]. For example, Onken et al discovered a gene expression prognostic signature that significantly improved the classification of uveal melanoma compared to traditional staging [15].…”

“…The resulting signature classified 268 primary cutaneous melanoma tumors into low-risk and high-risk groups, with 5–year disease–free survival rates of 97% and 31%, respectively [4]. This test is commercially available as a diagnostic tool called DecisionDx-Melanoma [29, 30], but it is not yet recommended by the National Comprehensive Cancer Network [10]. Its benefits to the patients must be confirmed using prospective clinical trials that include significantly larger cohorts with more representative metastatic characteristics [18, 31].…”

“…We hypothesized that there is room for significant improvement in the melanoma prognostic tests through rigid, unbiased, and comprehensive analysis of gene expression profiles [10, 32]. Accordingly, we applied a robust large-scale network analysis to the gene expression data of 404 samples from The Cancer Genome Atlas (TCGA) cohort of skin cutaneous melanoma [33].…”