Diagnostic and Prognostic Biomarkers in Melanoma

David Weinstein, MD, a Jennifer Leininger, MD,a Carl Hamby, PhD,b and Bijan Safai, MDa

Abstract

Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma.

Melanoma, an aggressive skin cancer, is currently the fifth most commonly diagnosed cancer in men and seventh in women in the United States with its incidence increasing 194 percent from 1975 to 2011.1,2 In 2014, approximately 76,100 patients will be diagnosed with melanoma in the United States, accounting for an estimated 9,710 deaths.1 Though recent advances in therapies for metastatic melanoma have shown some hope,3,4 melanoma with distant metastasis still carries a grim prognosis with a five-year survival rate of 16 percent.2 Given the poor prognosis for late stage melanoma, biomarkers are needed to aid in both the diagnosis and prognosis of melanoma and to determine which patients merit more aggressive therapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086529/

What you might be able to access openly:

Stage-specific prognostic biomarkers in melanoma

Cheng et al, 2015

Oncotarget. 2015 Feb; 6(6): 4180–4189.

Published online 2015 Jan 10. doi: 10.18632/oncotarget.2907

For convenience:  Abstract

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.

Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).

Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.

Keywords: prognostic biomarker, stage-specific, melanoma, BRAF, MMP

go to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414181/

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Another reference:   Review ARTICLE (open access)

KARAGIANNIS et al, 2015: Evaluating biomarkers in melanoma

Front. Oncol., 23 January 2015 | http://dx.doi.org/10.3389/fonc.2014.00383

go to: http://journal.frontiersin.org/article/10.3389/fonc.2014.00383/full

Best wishes and good luck !

Biomarkers in melanoma

H. Gogas1,*, A. M. M. Eggermont2, A. Hauschild3, P. Hersey4, P. Mohr5, D. Schadendorf6, A. Spatz7 and R. Dummer8

Abstract

Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques—DNA and RNA microarrays—have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers—lactate dehydrogenase, S100B and melanoma-inhibiting activity—as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future.

http://annonc.oxfordjournals.org/content/20/suppl_6/vi8.full

Three articles that could be of help.

Best regards

Robert

Thank you all for the useful information.

The following reference might be of interest: - 

Mohammed MQ, Abraha HD, Sherwood RA, MacRae K, Retsas S.

Serum S100beta protein as a marker of disease activity in patients with

malignant melanoma. Med Oncol. 2001;18(2):109-20.

Best Regards

Spyros Retsas