title: Immunohistochemical expression of VEGF, HIF1-a, and PlGF in malignant melanomas and dysplastic nevi.
abstract: We evaluated the role of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma angiogenesis and investigated their expression in dysplastic nevi, as potential melanoma precursors. In addition, we examined a possible correlation of VEGF expression with PlGF and HIF1-a. These factors were detected immunohistochemically in 95 melanomas of all types and stages and in 28 dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or control nevi. HIF1-a expression was more intense in melanocytes around necrotic areas but did not correlate with melanoma type, the Clark staging or the Breslow thickness. A strong positive association was detected between HIF1-a and VEGF expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in neoplastic cells of the controls. Its expression was more intense in melanomas, especially in nodular melanomas of elevated stage and thickness. PIGF was detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression did not correlate with melanoma staging nor thickness; however, it was more intense in superficial spreading melanomas, where a weak positive association between VEGF and PlGF was also detected. There was no association between HIF1-a and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a key role in melanoma progression; it activates VEGF secretion, which induces angiogenesis and metastasis. The role of PlGF seems to be limited.
authors.affiliation: Department of Dermatopathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Anagnostopoulou
authors.initials: A
authors.lastname: Konstantina
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Ioannidis
authors.forename: Anna
authors.initials: A
authors.lastname: Liossi
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Aroni
mesh_terms: D004416:Dysplastic Nevus Syndrome / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D051793:Hypoxia-Inducible Factor 1; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor