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. 2021 Feb 24;12(1):7–19. doi: 10.14740/wjon1349

Table 4. Genetic and Immunohistochemical Markers and Their Diagnostic Methods of Cutaneous Melanoma.

Method/marker Method description Reference
Comparative genomic hybridization (CGH) Accurate quantification of DNA copy number variations over a wide dynamic range with detection of single-copy deletions and duplications FFPE [54]
Analyses of allelic imbalance (AI) Detects the presence of deletions or gains of specific alleles [55]
Uses PCR amplification of microsatellite polymorphic markers followed by gel electrophoresis
Performed on DNA from formalin-fixed paraffin-embedded tissues (FFPE) tissues
Multiplex ligation-dependent probe amplification (MLPA) Measures the copy number of up to 45 nucleic acid sequences in one single reaction [56]
Performed on DNA extracted from routinely processed
Fluorescence in situ hybridization (FISH) Utilizes a fluorescent probe or group of probes to search for preselected genomic abnormalities in tumors [57]
Immunohistochemical markers
  S100A6 Part of the family of S100 proteins [58]
  PCNA A 36-kDa protein that is a cofactor of DNA polymerase d (expressed in all phases of cell cycle proliferation) [59, 60]
Proliferation marker
  Ki-67 Proliferation marker [61, 62]
  FLIP Immune modulatory marker [63]
  CD40 Immune modulatory marker-B-cell marker; also a tumor suppressor [64]
  CD26 Immune modulatory marker, an adenosine deaminase receptor [65]
  Cancer/testis antigens Immune modulatory marker [66]
Proteins that are aberrantly expressed in many types of malignancies
  Skp2 Cell cycle-related/anti-apoptosis markers [67]
F-box protein which aids the formation of a more massive protein complex that degrades p27
  Retinoblastoma protein (RB) Cell cycle-related/anti-apoptosis markers [68, 69]
  P53 Cell cycle-related/anti-apoptosis markers [69, 70]
  P21 Cell cycle-related/anti-apoptosis markers [6, 70]
  P16 Cell cycle-related/anti-apoptosis markers [61, 72, 73]
  HDM2 Cell cycle-related/anti-apoptosis markers [74]
90-kDa zinc finger protein that binds to p53 transcription activation domain inhibiting its function and targeting it for degradation by proteasomes
  GADD Cell cycle-related/anti-apoptosis markers [75]
Control transcription factors associated with cell cycle arrest, apoptosis, and cellular differentiation
  Cyclin D3 Cell cycle-related/anti-apoptosis markers [71]
  Cyclin B Cell cycle-related/anti-apoptosis markers [70, 71]
  Cyclin A Cell cycle-related/anti-apoptosis markers [70, 71]
  Cdk2 Cell cycle-related/anti-apoptosis markers [76]
  Bcl-2 Cell cycle-related/anti-apoptosis markers [77]
  Trk-A Signaling molecule [78]
Nerve growth factor receptor tyrosine kinase involved in activation of major oncogenic signaling pathways in melanoma, including the Ras/MAPK and phosphatidylinositol-3 kinase pathways
  PTEN Signaling molecule [71, 79]