Microvessel density, lymphovascular density, and lymphovascular invasion in primary cutaneous melanoma-correlation with histopathologic prognosticators and BRAF status

Hum Pathol. 2015 Feb;46(2):304-12. doi: 10.1016/j.humpath.2014.11.006. Epub 2014 Nov 26.

Abstract

The relationship between microvessel density (MVD), lymphovascular density (LVD), and lymphovascular invasion (LVI) in primary cutaneous melanoma (PCM) remains unclear. Given this, a total of 102 PCMs were assessed for MVD (vascular endothelial growth factor receptor 2 and Endocan), LVD (D2-40), and LVI (immunostaining with D2-40/S-100 and hematoxylin and eosin); tumoral S-100A13, vascular endothelial growth factor receptor 2, and Endocan; and BRAF status. LVD was associated with MVD (P = .01). MVD was higher in PCMs with depth greater than or equal to 2 mm and ulceration (P = .04, .05), whereas LVD was higher in PCMs with depth greater than or equal to 2 mm and mitoses (P = .03, .02). After adjusting for MVD and LVD, only ulceration was associated with LVI (P < .02). A BRAF mutation was seen in 30.4% cases, and when present, both LVD and host response (P = .0008 and .04, respectively) were significantly associated with MVD. Immunostaining with S-100A13 was noted in 99% of cases and a significant association noted only with ulceration (P = .05). Immunostaining increased LVI positivity (46.5% versus 4.9% by hematoxylin and eosin, P < .0001). MVD and LVD are not associated with LVI, appear to be closely related with each other, and are associated with select markers of poor prognosticative value. The association between a host response and LVD and MVD in PCMs with a BRAF mutation suggests that they exhibit potential for strategizing immunotherapies.

Keywords: BRAF; Histopathologic prognosticators; Lymphovascular density; Lymphovascular invasion; Microvessel density; Primary cutaneous melanoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Female
  • Humans
  • Lymphangiogenesis / physiology
  • Lymphatic Metastasis
  • Lymphatic Vessels / pathology*
  • Male
  • Melanoma / blood supply
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Microvessels / pathology*
  • Middle Aged
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Skin Neoplasms
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf