The role of VEGF-C staining in predicting regional metastasis in melanoma

Boone, Braden; Bacquer, D De; Pauwels, C; Naeyaert, Jean‐Marie; Brochez, Liève

doi:10.1097/00008390-200609001-00085

Cited by 13 publications

(33 citation statements)

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“…Dadras et al [12], on the other hand, detected moderate to high levels of cytoplasmatic VEGF-C in the majority of SLN-positive melanomas but in a minority of the SLN-negative melanomas (88.2% vs. 40.0%), and they found that tumour cell expression of VEGF-C may be useful to predict metastasis to the SLN. In addition, Bonne et al [19], in a study of 113 cases, found that high VEGF-C expression in melanoma cells was positively associated with the presence of a positive SLN. These discordant results highlight the need for yet more research in this field to determine the usefulness of VEGF-C expression in tumour cells from cutaneous melanoma as a predictive factor of node status in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

“…Positive VEGF-C staining in cutaneous melanoma is usually more frequent in macrophages than in melanoma cells [12,19]. Bonne et al [19] observed that VEGF-C expression in tumour-associated macrophages (TAMs) was strongly associated with the sentinel lymph node status, just like VEGF-C expression in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Bonne et al [19] observed that VEGF-C expression in tumour-associated macrophages (TAMs) was strongly associated with the sentinel lymph node status, just like VEGF-C expression in melanoma cells. This finding was not corroborated in our study, in which the SLNnegative and the SLN-positive cases showed a high level of positivity for VEGF-C in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Of these, VEGF-C and VEGF-D have been directly implicated in the promotion of lymphangiogenesis, via their binding to the receptor VEGFR-3 that is present in the lymph vessel endothelium [16]. In cutaneous melanoma, VEGF-C expression in tumour cells has been related with the stage of progression [17], and some data suggest that VEGF-C expression in primary skin melanoma may be predictive of lymph node metastasis dissemination [18,19]. However, VEGF-C is not only expressed in tumour cells; it is also expressed in tumour stroma cells, like macrophages and fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

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Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas

et al. 2011

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The dissemination of tumour cells to the lymph nodes is a complex process involving the formation of new lymph vessels, or lymphangiogenesis, produced by the tumour itself. The main growth factor involved in lymphangiogenesis is vascular endothelial growth factor C (VEGF-C), which is secreted by several different malignant tumours, including melanoma. Not only has VEGF-C expression been found in tumour cells, it has also been detected in tumour stromal cells like macrophages and fibroblasts. This study aimed to determine whether the expression of VEGF-C in tumour and stromal cells in cutaneous melanoma determines lymphangiogenesis and neoplastic dissemination to lymph nodes. We examined cases from 50 patients with melanoma who underwent selective biopsy of the sentinel lymph node. Immunohistochemical study was done with D2-40 to label lymph vessels, and the expression of VEGF-C was evaluated in tumour and stromal cells. Lymph vessel density was greater in sentinel lymph node-positive than in sentinel lymph node-negative cases, though the difference was not significant (P = 0.075). A significant correlation was seen between lymph vessel density and tumour thickness and the presence of ulceration. The main finding was that the expression of VEGF-C in fibroblasts was highly associated with the presence of metastasis in the sentinel node and with the Clark level. However, VEGF-C expression showed no relation in either tumour cells or macrophages with node status or other prognostic factors, such as the Breslow index or Clark level. Our results highlight the relevance of the stroma in tumour progression in cutaneous melanoma and its role in the spread to lymph nodes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas

et al. 2011

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“…The expression of VEGF-A and VEGF-C has been demonstrated to correlate with adverse clinicopathological variables in a variety of malignancies [14][15][16][17][18][19][20]. However, others studies showed no such correlation [21,22].…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor-A and -C: expression and correlations with lymphatic metastasis and prognosis in colorectal cancer

Mei

Lin

et al. 2010

Med Oncol

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Previous studies obtained contradicting results regarding the correlation between expression of VEGF-A, VEGF-C and colorectal cancer patients' clinicopathological features and prognosis. Moreover, the association between the growth factors' expression and lymphatic vessel invasion (LVI) with intratumoral and peritumoral difference has not been reported. In this study, 81 primary colorectal cancer samples were immunohistochemically stained for VEGF-A, VEGF-C and podoplanin. The expression of VEGF-A and VEGF-C in marginal portion was significantly higher than those in central portion (P = 0.000 for both). The expression of VEGF-A in marginal portion was correlated with lymph node metastasis (P = 0.031). The expression of VEGF-C in marginal portion was correlated with TNM stage (P = 0.045), peritumoral LVI (P = 0.048) and lymph node metastasis (P = 0.019). The group with high VEGF-A expression in marginal portion showed worse survival than the low expression group (P = 0.039). Patients with high expression of VEGF-C in the marginal portion were not significantly different from those with low VEGF-C expression (P = 0.121). Patients with high expression of both VEGF-A and VEGF-C in the marginal portion showed the worst survival (P = 0.015). In conclusion, increased expression of VEGF-A and VEGF-C in marginal portion of colorectal cancer was correlated with lymph node metastasis. VEGF-C facilitates colorectal cancer cells invade into peritumoral lymphatic vessels, and different mechanisms may exist in the invasion of tumor cells into peritumoral and intratumoral lymphatic vessels. Assessment the expression of both VEGF-A and VEGF-C in the marginal portion of tumor may help to identify patients with colorectal cancer with unfavourable overall survival.

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Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma

et al. 2019

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The high mortality rate of melanoma is broadly associated with its metastatic potential. Tumor cell dissemination is strictly dependent on vascularization; therefore, angiogenesis and lymphangiogenesis play an essential role in metastasis. Hence, a better understanding of the players of tumor vascularization and establishing them as new molecular biomarkers might help to overcome the poor prognosis of melanoma patients. Here, we further characterized a linear murine model of melanoma progression and showed that the aggressiveness of melanoma cells is closely associated with high expression of angiogenic factors, such as Vegfc , Angpt2, and Six1, and that blockade of the vascular endothelial growth factor pathway by the inhibitor axitinib abrogates their tumorigenic potential in vitro and in the in vivo chicken chorioallantoic membrane assay. Furthermore, analysis of The Cancer Genome Atlas data revealed that the expression of the angiogenic factor ANGPT2 ( P ‐value = 0.044) and the lymphangiogenic receptor VEGFR‐3 ( P ‐value = 0.002) were independent prognostic factors of overall survival in melanoma patients. Enhanced reduced representation bisulfite sequencing‐based methylome profiling revealed for the first time a link between abnormal VEGFC , ANGPT2, and SIX1 gene expression and promoter hypomethylation in melanoma cells. In patients, VEGFC ( P ‐value = 0.031), ANGPT2 ( P ‐value < 0.001), and SIX1 ( P ‐value = 0.009) promoter hypomethylation were independent prognostic factors of shorter overall survival. Hence, our data suggest that these angio‐ and lymphangiogenesis factors are potential biomarkers of melanoma prognosis. Moreover, these findings strongly support the applicability of our melanoma progression model to unravel new biomarkers for this aggressive human disease.

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The role of VEGF-C staining in predicting regional metastasis in melanoma

Cited by 13 publications

References 0 publications

Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas

Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas

Vascular endothelial growth factor-A and -C: expression and correlations with lymphatic metastasis and prognosis in colorectal cancer

Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma

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