Predominant formation of heavily pigmented dermal melanocytomas resembling 'animal-type' melanomas in hepatocyte growth factor (C57BL/6 x C3H)F1 mice following neonatal UV irradiation

J Cutan Pathol. 2007 Sep;34(9):667-74. doi: 10.1111/j.1600-0560.2006.00679.x.

Abstract

Background: Transgenic mice expressing hepatocyte growth factor (HGF) develop cutaneous melanocytic tumors following neonatal UV exposure. Here, we examined the histologic spectrum of UV-induced melanocytic tumors in HGF mice on a pigmented (C57BL/6 x C3H/HeN)F(1) background.

Methods: Neonatally irradiated (4000 J/m(2)) mice were monitored for 43 weeks, and 31/34 (91%) animals developed a total of 163 melanocytic tumors.

Results: Of 54 primary tumors analyzed, most (49/54, 91%) demonstrated exclusively dermal collections of epithelioid cells with voluminous densely pigmented cytoplasm. Seven of these also demonstrated a population of spindled cells with mitoses. Several (3/54, 6%) tumors exhibited a junctional component with melanocytes present in the epidermis. Staining with PEP8 confirmed the presence of interfollicular melanocytes at the dermal-epidermal junction in neonatal skin.

Conclusions: In contrast to HGF animals on an albino (FVB) background, HGF animals on the pigmented (C57BL/6 x C3H/HeN)F(1) background do not develop classic radial growth phase melanoma but rather predominantly develop dermal melanocytomas resembling the 'animal-type' melanoma occasionally seen in humans. These results demonstrate the influence of genetic background on histologic pattern of UV-induced melanomas in mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers, Tumor / metabolism
  • Epithelioid Cells / pathology
  • Epithelioid Cells / radiation effects
  • Female
  • Genotype
  • Hepatocyte Growth Factor / genetics*
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanocytes / radiation effects
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / metabolism
  • Neoplasms, Radiation-Induced / pathology*
  • Skin / radiation effects*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Species Specificity
  • Ultraviolet Rays*

Substances

  • Biomarkers, Tumor
  • Hepatocyte Growth Factor