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.

Association of vascular endothelial growth factor expression with patohistological parameters of cutaneous melanoma

“…We found that 5 out of 81 patients with melanoma (2 in stage I, 2 in stage II and 1 in stage III) were completely negative to VEGF (5.7%). In the study of Konstatina et al 28 from 2011, 13.69% patients with melanoma were negative for VEGF, but, in contrast with our control group results, 75% of patients with dysplastic nevi had weak VEGF staining. The opinions on VEGF positivity in benign melanocytic lesions are divided.…”

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients

“…Similarly, targeting HIF-1α-related pathways may attenuate cardiovascular and metabolic consequences of IH ( 46 – 50 ). Thus, it is reasonable to assume that increased HIF-1α expression in the context of sleep-disordered breathing in our cohort would lead to increased HIF-1α expression in tissues in general and more specifically in the CM lesions, where its transcriptional activity could have fostered increased proliferation and other aggressiveness indicators ( 14 – 16 ). In contrast, the absence of any significant association between VEGF expression in the CM sections and correlates of nocturnal hypoxemia was surprising.…”

Hypoxia‐inducing factors as master regulators of stemness properties and altered metabolism of cancer‐ and metastasis‐initiating cells

“…Importantly, high expression levels of HIF‐1α, HIF‐2α and their target genes such as VEGF, have also been detected in melanoma cells in up to 80% cases of primary and metastatic melanoma specimens from patients, and more particularly at the margin of necrotic areas of tumours, and associated with melanoma progression as well as a poor prognosis of patients . Moreover, a nuclear staining for pluripotency‐associated transcription factor Oct‐3/4 was also seen in a small subset of melanoma cells, and particularly in hypoxic cancer cells near necrotic areas within primary melanomas in vertical growth phase or metastatic melanoma tissue specimens .…”