Patient case: 62-year-old female with mucosal melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Repigmentation Patterns Induced by NB-UVB and Their Relationship With Melanocytic Migration in Vitiligo

Summary: Vitiligo is the most common acquired depigmented disorder of the skin characterized by destruction of melanocytes resulting in well-circumscribed achromic macules. Ultraviolet phototherapy with narrow band (UVB-NB) is currently one of the treatments of choice, because it is able to induce proliferation, differentiation, maturation and migration of melanocytes. This repigmentation has distinctive patterns such as follicular, marginal, and diffuse. The aim of this study is to observe the dynamics of migration and proliferation, in vitiligo patients under UVB radiation phototherapy treatment. The investigators will evaluate this process by measuring FAK (focal adhesion kinase ) and c-Kit by immunohistochemistry and reverse transcriptase polymerase chain reaction assay.

Detailed description: Vitiligo is the most common acquired depigmented disorder of the skin characterized by destruction of melanocytes, which results in well-circumscribed achromic macules. Its etiology is not fully recognized but functional melanocytes may disappear by autoimmune response, oxidative stress that induces melanocytes apoptosis, and loss of cell-cell adhesion between melanocytes and keratinocytes.
  Ultraviolet phototherapy with narrow band (UVB-NB) is currently one of the treatments of choice with an average response rate of 60-70% on lesions. UVB-NB phototherapy may induce immune regulation and melanogenic induction. It is also able to induce Treg cells proliferation to suppress the autoimmune response which destroys melanocytes. By the other hand, UVB-NB induces signaling of proliferation, differentiation, maturation and migration of melanocytes, playing an important role in vitiligo re-pigmentation.
  Phosphorylation of focal adhesion kinase (p-FAK125) is a cytoplasmic tyrosine kinase that plays as an important component in the signal transduction of cell migration, as it modulates cytoskeletal proteins necessary for their movement. UVB-NB radiation induces migration on melanocytes cultures increasing their levels of p-FAK125 and it has been proposed as a melanocyte migration marker.
  C-kit is a tyrosine kinase receptor expressed on melanoblasts and differentiated melanocytes. Ligand binding induces PI3K, MAPK and Src kinase pathways, which traduce differentiation of melanoblast into proliferating melanocytes; so its expression imply the presence of mature pigmented melanocytes. C-kit is increased in mature melanocytes after UVB exposure, but it has been show that in melanoma cases the loss of c-kit expression is involved in cancer progression , therefore c-kit signaling is also associated in migratory process. Although, different reports have been established the expression of this markers on vitiligo, is not defined this markers on the repigmentation patterns induces to UVB radiation.
  UVB radiation induces repigmentation in distinctive patterns such as follicular, marginal, and diffuse. Follicular pattern is the predominant, and comes from hair follicle melanocytes. In the marginal pattern melanocytes from healthy skin are attracted to the lesion. In the diffuse pattern UVB radiation stimulates those inactive melanocytes. In contrast, achromic pattern not induces melanocyte activation. The relation between the biological behavior of melanocytes and these repigmentation patterns, may provide insights to an improved method to treat vitiligo. The aim of this study is to observe the dynamic of migration and proliferation by specific markers on the repigmentation patterns of vitiligo patients under UVB radiation phototherapy.

Eligibility: Inclusion Criteria:
  -  Symmetric vitiligo
  -  Affected body surface greater than 15%
  -  Patients with follicular, marginal and diffuse repigmenting patterns
  -  No previous topical or systemic treatment
  -  Signed informed consent
  Exclusion Criteria:
  -  Concomitant treatment or systemic diseases
  -  Pregnancy
  -  Drugs intake
  -  Mental disorders

Relevance to patient case: not relevant