Prognostic value of tumour vascularity in primary melanoma

Ilmonen, Suvi; Kariniemi, Arja‐Leena; Vlaykova, Tatyana; Muhonen, Timo; Pyrhönen, Seppo; Asko‐Seljavaara, Sirpa

doi:10.1097/00008390-199906000-00009

Cited by 36 publications

(29 citation statements)

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“…More surprisingly, a similar immunohistochemical analysis of primary cutaneous melanomas samples taken from 84 patients showed that the only independent variable associated with disease-free survival was tumor thickness (Breslow classification). The only variable associated with overall survival was depth of tumor infiltration (Clark classification), whereas high levels of vascularity were actually correlated with survival (Ilmonen et al, 1999).…”

Section: Tumor Angiogenesis In Melanomamentioning

confidence: 97%

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit¹,

2003

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The induction of angiogenesis is a critical point in the development of most human tumors -including melanomas. Some of the earliest studies in the field of tumor angiogenesis showed that transplantation of human melanoma fragments into the hamster cheek pouch stimulated blood vessel growth. Since then, numerous studies have demonstrated that human melanomas also induce angiogenesis. The prognostic importance of the degree of melanoma vascularization, however, has remained controversial. Elevated expression of several angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8, has been detected in primary cutaneous melanomas, and the importance of these mediators in promoting melanoma angiogenesis and metastasis has been confirmed in tumor xenotransplant models. Based upon these findings, several clinical trials of angiogenesis inhibitors have been initiated in human melanoma patients and are currently underway. Recent experimental evidence indicates that tumorassociated lymphangiogenesis also plays an important role in mediating tumor spread to regional lymph nodes. These observations have important implications for prognosis and treatment of human melanomas.

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Section: Tumor Angiogenesis In Melanomamentioning

confidence: 97%

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit¹,

2003

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“…On the other hand, some investigators 73,74 report an association between high "vascularity" and outcome in cutaneous melanoma while Ilmonen et al 75,76 recently reported that high vascularity was associated with a favorable outcome.…”

Section: Counting Microvessels and Vasculogenic Mimicrymentioning

confidence: 99%

Vasculogenic Mimicry and Tumor Angiogenesis

Folberg

Hendrix

Maniotis

2000

The American Journal of Pathology

629

434

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Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis-the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed "vasculogenic mimicry" to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases. Tumors require a blood supply to sustain growth. The tumor microcirculation plays a central role in the hematogenous dissemination of cancers. Considerable attention has been focused on the mechanisms by which tumors acquire their blood supply. It is a well-accepted paradigm that tumors recruit new blood vessels from the existing circulation 1 -angiogenesis-either from factors secreted by the tumor cells, as Folkman 2,3 has emphasized, or from surrounding stromal cells. 4 There are two variations on the theme of tumor angiogenesis: augmentation of the angiogenic response by progenitor endothelial cells, and vessel cooption. Asahara and associates 5 described the incorporation of endothelial cell progenitors (or angioblasts) from circulating peripheral blood into sites of ischemic-driven angiogenesis. Holash and associates 6 described a process of "vessel cooption" in which tumors coopt the existing vasculature, which regresses leading to massive necrosis, and the tumor is then vascularized at the periphery by tumor angiogenesis as described above.We 7 recently described a novel process by which tumors develop a highly patterned microcirculation that is independent of angiogenesis: in aggressive primary and metastatic melanomas, the tumor cells generate acellular microcirculat...

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“…The unique topology of VM distribution is consistent with the notion that specific molecular and cellular modifications occur, which facilitate tumor invasion and growth. Therefore, VM is a poor prognosis indicator in patients with sarcomas and melanomas (21)(22)(23).…”

Section: 08 --------------------------------------------------------mentioning

confidence: 99%

Microcirculation patterns in different stages of melanoma growth

et al. 2006

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Abstract. Several microcirculation patterns in tumors have been reported, including vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels. To investigate the sources of blood supply during different tumor stages, we studied the correlation between expression of vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels in a mouse melanoma xenograph. Sixty C57 mice were divided into 12 groups (5 mice per group) and inoculated with B16 melanoma cells. Eleven days later, the average tumor size was approximately 0.2 to 0.3 cm. From days 11 to 22, one group per day was randomly sacrificed, and the density of vasculogenic mimicry, mosaic vessels and endothelium-dependent vessels was measured in tumor tissue sections. Immunohistochemical dual-staining and electronic microscopy were also used to confirm the vessel types. All three types of microcirculation patterns were observed during tumor development. In the early stage of tumor growth, vasculogenic mimicry is the main pattern of blood supply. As the area of tumor tissue expands and the number of endothelium increase, vasculogenic mimicry is replaced by endothelium-dependent vessels. Mosaic vessels might be the interim state between vasculogenic mimicry and endothelium-dependent vessels. The number of endothelium-dependent vessels correlated with the size of the tumor (r=0.718, P=0.009), while the number of vasculogenic mimicry was inversely correlated (r=0.77, P=0.003). In conclusion, the number of vasculogenic mimicry decreased and the number of endothelial-dependent vessels increased during tumor growth. IntroductionTo maintain development and rapid growth, tumors need a sufficient blood supply (1). Besides the well-studied angiogenesis, recent studies have revealed several new patterns by which tumor tissues nourish themselves, including the pattern of mosaic vessels from both endothelium and tumor cells (2,3), and the pattern of vessels lined exclusively with tumor cells mimicking the presence and function of endothelial cells. This last process is termed vasculogenic mimicry (4,5).Three patterns of microcirculation were reported to participate in tumor blood supply. However, it is unclear how these patterns are involved in tumor growth. To answer this question, we monitored blood supply patterns during different stages of growth of melanoma xenografts in C57 mice. The results demonstrate that there are specific microcirculation pattern traits in different stages of tumor growth. Vasculogenic mimicry is the dominant blood supply pattern in the early stage characterized by rapid tumor growth (6). When the tumor mass expands, endothelial cells differentiate and proliferate, and the mosaic vessels appear as a transitional pattern. Consequently, endothelium-dependent vessels replace vasculogenic mimicry and mosaic vessels to become the major pattern of blood supply in the late stage of tumor growth (7,8). Materials and methodsAnimals. Sixty C57/6J 6-8 week-old black mice including 30 males and 30 females were purchase...

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Prognostic value of tumour vascularity in primary melanoma

Cited by 36 publications

References 0 publications

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Vasculogenic Mimicry and Tumor Angiogenesis

Microcirculation patterns in different stages of melanoma growth

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