Introduction Biomarkers play an important role in the diagnosis and prognostic classification of various cancer entities and can moreover be useful in monitoring the patient’s clinical course of disease and response to therapy. In general, biomarkers are proteins, less often carbohydrates or lipids, and their expression profiles are associated with malignant disease. In the majority of cases, the marker molecules are expressed by the tumour cells themselves or by cells of the tumour microenvironment. Thus, most biomarkers can primarily be found in malignant tissues, but after active secretion or passive release at tumour cell destruction also become detectable in body fluids like blood, lymph or urine. Besides morphological and histopathological biomarkers (anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression, as well as proteomic profiling data, indicates new candidate molecules involved in skin cancer pathogenesis, which may after further validation represent new markers superior to existing ones. This ongoing process of biomarker identification and validation would result in a rapidly changing molecular view and classification of skin cancers. Malignant melanoma Serologic markers of malignant melanoma 1 1 Table 1 Serologic markers of malignant melanoma  Serologic marker Selected literature Melanocyte lineage/differentiation antigens S100-beta 30 71 32 33 18 43 28 MIA (melanoma inhibitory activity) 9 8 10 74 28 Tyrosinase 2 5-S-Cysteinyldopa 91 34 L-Dopa/L-tyrosine 75 Proangiogenic factors VEGF (vascular endothelial growth factor) 83 56 12 BFGF (basic fibroblast growth factor) 83 12 IL-8 (Interleukin-8) 68 83 12 Molecules involved in cell adhesion and motility sICAM-1 (soluble intracellular adhesion molecule 1) 34 87 94 sVCAM (soluble vascular cell adhesion molecule 1) 26 87 Matrix metalloproteinases (MMP)-1 and 9 63 53 Cytokines and cytokine receptors IL-6 (Interleukin-6) 50 73 IL-10 (Interleukin-10) 21 51 sIL-2R (soluble interleukin-2-receptor) 11 58 HLA molecules sHLA-DR (soluble HLA-DR) 62 sHLA-class-I (soluble HLA-class I) 89 Others LDH (lactate dehydrogenase) 72 18 6 CRP (C-reactive protein)  19 Albumin 72 TuM2-PK (Tumour pyruvate kinase type M2) 81 sFas/CD95  84 YKL-40 69 70 CYT-MAA (cytoplasmic melanoma-associated antigen) 85 HMW-MAA (high-molecular-weight melanoma-associated antigen) 85 Fig. 1 MIA  49 59 30 9 8 18 43 36 2 71 33 74 32 1 Fig. 2 P  18 6 1 1 46 Immunohistochemical markers of malignant melanoma Cutaneous malignant melanoma regularly develops from the radial to the vertical growth phase and thereafter to metastatic disease. The variability of this clinical course is only partially explained by morphological and histopathological parameters like primary tumour localization, patient gender and age, mitotic rate, tumour thickness and ulceration. There is a need to identify molecular variables, which help to assign patients to specific risk groups. The number of modalities for diagnosing and subclassifying malignant melanomas is rapidly increasing and includes immunohistochemistry of tissue sections and microarrays, gene expression profiling, comparative genomic hybridization and mutational analysis. These methodologies promise to improve our prognostic classification systems, as well as our diagnostic and therapeutic potential. 44 2 Table 2 Immunohistochemical markers of malignant melanoma associated with prognosis  Association with poor prognosis Selected literature Melanocyte lineage/Differentiation antigens  gp100/HMB45 Increased expression 52 Tumour suppressors/oncogenes/signal transducers INK4A Decreased expression 47 3  PTEN Decreased expression 48  pRb (retinoblastoma protein) Inactivation due to protein phosphorylation 65  EGFR (epidermal growth factor receptor) Increased expression 80  p-Akt (activated serine-threonine protein kinase B) Increased expression 17  c-Kit Expression 35 82  c-myc Increased expression 42  AP-2 (activator protein-2alpha) transcription factor Loss of nuclear AP-2 expression 7  HDM2 (human homologue of murine mdm2) Increased expression 61 bcl-6 Expression 3 Cell cycle associated proteins  Ki67 (detected by Mib1) Increased expression 29 3 57  Cyclin A, B, D, E Increased expression 24 25 CIP1 Decreased expression 3  Geminin Increased expression 92  PCNA (proliferating cell nuclear antigen) Increased expression 92 Regulators of apoptosis  bcl-2 Increased expression 78  bax  Decreased expression 23  Bak Decreased expression 23  APAF-1 (Apoptotic protease activating factor-1) Decreased expression 27  Surviving Increased expression 78 Molecules involved in angiogenesis  LYVE-1 (lymphatic vascular endothelial hyaluronan receptor-1)  Increased expression 16  PTN (pleiotrophin) Increased expression 93 Molecules involved in cell adhesion and motility  P-Cadherin Strong cytoplasmic expression 5  E-Cadherin Decreased expression 4  Beta-catenin Loss of nuclear staining 5  Integrins beta1 and beta3  Increased expression 66  MMPs (matrix metalloproteinases) Increased expression 63  Dysadherin Increased expression 54  CEACAM1 (carcinoembryonic-antigen-related cell-adhesion molecule 1) Increased expression 79  Osteonectin (also termed BM40 or SPARC (secreted protein, acidic and rich in cysteine)) Increased expression 45 Others   TA (telomerase activity)  Increased expression 13  Melastatin Decreased expression 22  ALCAM/CD166 (Activated leukocyte cell adhesion molecule) Increased expression 77  CXCR4 receptor Increased expression 67  Metallothionein Increased expression 88 92 92 Squamous cell carcinoma of the skin 60 76 41 41 76 37 38 64 64 55 Cutaneous T-cell lymphomas 90 20 40 39 86 86 31 Conclusion and future directions 14 15