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Updated: Jun 21, 2026

Quantification of Hypopigmentation Activity In Vitro
06:08

Quantification of Hypopigmentation Activity In Vitro

Published on: March 6, 2019

Melanoma hyperpigmentation is strongly associated with KIT alterations

Julie M Wu1, Hector Alvarez, Patricia García

  • 1Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

The American Journal of Dermatopathology
|August 5, 2009
PubMed

Insights

KIT alterations are linked to melanoma, particularly in hyperpigmented tumors with vertical growth. This finding may help identify patients who could benefit from targeted therapies.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • KIT alterations are implicated in melanoma pathogenesis.
  • Imatinib treatment shows some efficacy, but KIT's role in melanoma histology is unclear.
  • Understanding KIT's relationship with histological features is crucial for targeted therapy selection.

Purpose of the Study:

  • To investigate the association between KIT protein expression and various melanoma histological features.
  • To determine the correlation of KIT alterations with clinical and pathological variables.
  • To identify histological indicators that may predict KIT aberrations in melanoma.

Main Methods:

  • Evaluated KIT protein expression via immunohistochemistry in 70 melanoma cases.
  • Analyzed KIT expression against histological variables: subtype, sun damage, tumor-infiltrating lymphocytes, in situ component, vertical growth phase (VGP), location, and hyperpigmentation.
  • Performed mutational analyses for KIT exons 9 and 11, and BRAF on cases with high KIT expression.

Main Results:

  • High KIT expression (3+ membranous staining) was observed in 28 cases.
  • Significant univariate associations included inverse relationships with sun damage and VGP, and correlations with tumor location, subtype, and hyperpigmentation.
  • Multivariate analysis identified hyperpigmentation (P = 0.002) and VGP (P = 0.019) as statistically significant predictors of high KIT expression.
  • KIT mutations were uncommon (2/27 in exon 11), with only one BRAF V600E mutation found.
  • The frequency of KIT aberrations increased to 40% in cases with hyperpigmentation and VGP.

Conclusions:

  • KIT aberrations are not limited to acral or mucosal melanomas.
  • There is an inverse relationship between KIT abnormalities and sun damage.
  • Hyperpigmentation is a strong predictor of KIT aberrations, overriding other histological factors.
  • Histological features like hyperpigmentation and VGP can help identify melanomas with potential KIT aberrations for further investigation and targeted therapy.

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