title: Microvessel density, lymphovascular density, and lymphovascular invasion in primary cutaneous melanoma-correlation with histopathologic prognosticators and BRAF status.
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.
authors.affiliation: Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA 02118. Electronic address: aungpatho@gmail.com.
authors.forename: Phyu Phyu
authors.initials: PP
authors.lastname: Aung
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118. Electronic address: nleone@bu.edu.
authors.forename: Dominick
authors.initials: D
authors.lastname: Leone
authors.affiliation: Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA 02118. Electronic address: j.kyle.feller@gmail.com.
authors.forename: John Kyle
authors.initials: JK
authors.lastname: Feller
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118. Electronic address: shiyang@bu.edu.
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Dermatology, UT Southwestern Medical Center, Dallas, TX 75390. Electronic address: marierhernandez@gmail.com.
authors.forename: Marier
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Aurora Diagnostics, Greensboro, NC 27408. Electronic address: ryaar@alum.bu.edu.
authors.forename: Ron
authors.initials: R
authors.lastname: Yaar
authors.affiliation: Departments of Dermatology and Pathology, Mt Sinai School of Medicine, New York, NY 10029. Electronic address: skinpathology@gmail.com.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Dermatology, State University of New York at Buffalo, Buffalo, NY 14203. Electronic address: thelm@buffalomedicalgroup.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helm
authors.affiliation: Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA 02118. Electronic address: mmahalin@bu.edu.
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D012878:Skin Neoplasms; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Histopathologic prognosticators; Lymphovascular density; Lymphovascular invasion; Microvessel density; Primary cutaneous melanoma