**1. Introduction**

The incidence of cutaneous malignant melanoma (CMM) is increasing in the Western world, despite the implementation of prevention campaigns for several years. Early detection, targeted at-risk populations helps to identify patients with beginning melanoma lesions, but despite these efforts, many patients - often young,- present with thicker tumors (with a higher Breslow, over 1mm - Breslow is a measurement in mm of the vertical thickness of the primary tumor-). [1]

A late diagnosis is also often associated with a greater Breslow thickness index and a greater risk for invasion of regional lymph nodes (stage III), or distant metastatic lesions (stage IV) [2]. CMM usually progresses from an in situ proliferation in a radial growth pattern. Then appears the vertical growth phase which is a major event for the dissemination of cells, as it allows cells to migrate deeper into the dermis, the lymphatic vessels and blood flow.

In the seventh revision of the American Joint Committee on Cancer (AJCC) staging for melanoma (2009), patients can be divided into four stages: stage I and II disease (local) stage III (locoregional disease) and stage IV (metastatic disease). In this ranking, the only serum marker that was built for clinical use is the lactate dehydrogenase (LDH) as the serum LDH was confirmed in multivariate analysis to be an independent predictor even after taking into account site and number of metastases [2]. The value of LDH is still often discussed in local/ locoregional conditions.

Surgery is the mainstay of treatment of melanoma. The major concern after diagnostic excision of the primary lesion is whether CMM has already metastasized or not. Indeed many argu‐ ments emphasize that early detection of melanoma metastases may improve the prognosis of

© 2013 Vereecken; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

as proteins, peptides, DNA, mRNA. Interest is the fact that these markers can be found in the tissues, cells and / or body fluids. Also viable melanoma cells can also be found in the peripheral blood of melanoma patients. We limit ourselves in this article to the description of serum

Serum Markers in Clinical Management of Malignant Melanoma

http://dx.doi.org/10.5772/55530

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The ideal biomarker should be a molecule easily detectable in the serum of a patient who presents a growing tumor. The biomarker should have a sufficient sensitivity and specificity to minimize false negatives and false positives. Sensitivity refers to the proportion of patients with confirmed disease who have a positive test for a biomarker, whereas specificity can be defined as the proportion of healthy individuals with a negative test. Previous studies have shown that many molecules that may be involved in oncogenesis and cancer spread can be found in the serum of cancer patients in particular patients with melanoma, but their sensitivity and / or specificity are still debatable. These molecules can be produced and secreted or excreted into the bloodstream directly by melanoma cells or indirectly by destruction of

Below, we detail the most important molecules in serum that have been described as a

As mentioned above, this enzyme has been considered as the main serum prognostic param‐ eter in patients with metastatic melanoma (AJCC stages III and IV). Numerous studies have validated LDH as the factor most predictive of patient outcome, and this independently and statistically significant. This led to a stratification of the AJCC :patients with metastatic melanoma with high levels of LDH are designated as M1c whatever the site of metastasis [2]. Note, however, that Hamberg stated that in a series of 53 patients with stage IV AJCC melanoma only 38% had elevated LDH, suggesting that elevated LDH is not the ideal marker for this condition [4]. Moreover, in a multivariate analysis of 64 patients with AJCC stage IV melanoma Hauschild has failed to demonstrate the independent prognostic value of LDH [5]. It should be recalled that the LDH assay can be falsely positive due to hemolysis and other

However, Weide et al also insist in a study of 855 patients on the prognostic value of LDH [6].

CRP is a nonspecific inflammatory parameter that may have a role in the detection of mela‐ noma progression. This protein is produced by hepatocytes as acute phase response of non-

Elevated serum CRP was associated with a poor prognosis in various cancers. Deichmann et al. analyzed the prognostic significance of CRP compared to the LDH patients AJCC stage IV

melanoma cells by chemotherapy, immunotherapy or combination therapy [3].

molecular markers in CMM.

biomarker for CMM.

**2. Main serum markers in CMM**

**2.1. Lactate Dehydrogenase (LDH)**

factors, including hepatitis.

**2.2. C-Reactive Protein (CRP)**

specific inflammatory processes.

**Figure 1.** Breslow index measures in mm the thickness of the lesion

patients, at least for some of them. To date, no marker for early detection of melanoma metastases is unanimously recognized.

A melanoma patient around high risk (high risk of recurrence) can be defined as a patient with a 50% risk of relapse within up to 10 years, despite optimal initial surgical treatment. These high-risk patients should be carefully monitored and treated if possible with adjuvant therapeutic strategies. Interferon-α and, more recently, ipilimumab have been proposed as adjuvant therapies, but their effect on survival is still a matter of debate. To date, no predictive marker of response has been described.

The metastatic process involves the spread of cancer cells in locoregional or distant anatomic sites via the lymphatics and / or blood flow. In the case of melanoma, circulating cells can find a suitable microenvironment in the sentinel node (the first lymph drainage lymph node area), other lymph nodes or distant organs (lymph nodes, liver, lungs, brain, bone).

In fact, the understanding of the biology and mechanism of metastatic cascade provides new molecular targets and can help us to discover new biomarkers. Biomarkers can be divided into diagnostic markers for disease detection and prognostic and predictive markers, which should predict response to treatment. Cancer biomarkers consist of many molecular structures such as proteins, peptides, DNA, mRNA. Interest is the fact that these markers can be found in the tissues, cells and / or body fluids. Also viable melanoma cells can also be found in the peripheral blood of melanoma patients. We limit ourselves in this article to the description of serum molecular markers in CMM.

The ideal biomarker should be a molecule easily detectable in the serum of a patient who presents a growing tumor. The biomarker should have a sufficient sensitivity and specificity to minimize false negatives and false positives. Sensitivity refers to the proportion of patients with confirmed disease who have a positive test for a biomarker, whereas specificity can be defined as the proportion of healthy individuals with a negative test. Previous studies have shown that many molecules that may be involved in oncogenesis and cancer spread can be found in the serum of cancer patients in particular patients with melanoma, but their sensitivity and / or specificity are still debatable. These molecules can be produced and secreted or excreted into the bloodstream directly by melanoma cells or indirectly by destruction of melanoma cells by chemotherapy, immunotherapy or combination therapy [3].

Below, we detail the most important molecules in serum that have been described as a biomarker for CMM.
