Microvascular Loops and Networks as Prognostic Indicators in Choroidal and Ciliary Body Melanomas

Mäkitie, Teemu; Summanen, Paula; Tarkkanen, Ahti; Kivelä, Tero

doi:10.1093/jnci/91.4.359

Cited by 144 publications

(88 citation statements)

References 25 publications

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“…7 Furthermore, the pattern of CD34 immunoreactivity matches the pattern of Factor VIII staining regardless of whether PAS staining is present. 7,9 The apparent similarity of PAS staining to the staining pattern of the endothelial cell marker Ulex europeus agglutinin I lectin, as reported by Folberg, 4 is likely to be an artifact of connective tissue autofluorescence. 8 Maniotis et al report that the PAS-stained pattern in tissue sections precisely matches the microvascular architecture seen in angiograms.…”

Section: Pas-stained Network In Uveal Melanomas Do Not Reflect the Mmentioning

confidence: 69%

Vasculogenic Mimicry: How Convincing, How Novel, and How Significant?

McDonald

Munn

Jain

2000

The American Journal of Pathology

164

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Section: Pas-stained Network In Uveal Melanomas Do Not Reflect the Mmentioning

confidence: 69%

Vasculogenic Mimicry: How Convincing, How Novel, and How Significant?

McDonald

Munn

Jain

2000

The American Journal of Pathology

164

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“…The statistical association between the histological presence of microcirculatory loops and networks and death from metastatic melanoma has been confirmed by independent laboratories. 8,30,31 We found subsequently that loops and networks are not found in uveal nevi, 32 that networks tend to localize preferentially to the periphery of the tumor (the tumor growth zone), 33 that the amount of tumor remodeling by looping patterns (the percentage of area occupied by these patterns on a two-dimensional tissue section) had a negative effect on patient survival, 10 and that the classification of tumors into high-and low-risk for metastasis was likely to be consistent regardless of the tissue plane sampled within a large tumor. 34 These PAS-positive patterns were presumed to be associated with the tumor microcirculation for several reasons.…”

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

“…31 In light of the absence of demonstrable endothelial cells by light and transmission electron microscopy in the matrix-associated vascular channels, we further evaluated the distribution of endothelial markers within these patterns.…”

Section: Immunohistochemical Profile Of Melanoma Intratumoral Patternmentioning

confidence: 99%

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Maniotis

Folberg

Hess

et al. 1999

The American Journal of Pathology

1,755

1,636

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Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy , by transmission electron microscopy , or by using an immunohistochemical panel of endothelial cell markers (Factor VIIIrelated antigen , Ulex , CD31 , CD34 , and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in threedimensional cultures containing Matrigel or dilute Type I collagen , without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye , highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions , even after the addition of conditioned medium from metastatic pattern- It is generally assumed that tumors require a blood supply for growth and metastasis. 1 The development of the tumor microcirculation compartment includes both the production of new blood vessels (angiogenesis) and their remodeling. 2 In fact, the number of vessels 3 and the patterning of the microcirculation 4 by remodeling events are used as histological markers of tumor progression. Although attention has been focused on factors that stimulate and suppress tumor angiogenesis, the molecular mechanisms underlying tumor remodeling remain enigmatic. It is therefore critical to investigate remodeling of the intratumoral microvasculature in various tumor models.Melanoma is among the better characterized tumor models with respect to prognostic staging of disease progression. The rising incidence of cutaneous melanoma makes this tumor an important public health problem. Melanoma of the interior of the eye, uveal melanoma, although much less common than cutaneous melanoma, poses a threat to vision and significant morbidity; nearly 50% of patients with uveal melanoma die from metastatic melanoma. 5 Cutaneous melanoma may disseminate through lymphatics or blood vessels. In contrast, the interior of the eye lacks lymphatics, and uveal melanoma, which develops in one of the most capillary-rich tissues of the body, is a paradigm for pure hematogeneous dissemination of cancer. 6 Therefore, the development of a tumor microcirculation in uveal melanoma is a rate-limiting step for hematological metastasis and serves as an important model for study of the cellular and molecular infrastruc-

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“…35 The presence of so-called vascular mimicry patterns, whose detection is enhanced by staining with periodic acid-Schiff, also carries a poorer prognosis. 36,37 These patterns initially were called vascular loops and networks or extracellular matrix patterns. Tumors that have extended extrasclerally, have invaded the lumen of a vortex vein, or invaded the subarachnoid space of the optic nerve are also considered to have poorer prognosis.…”

mentioning

confidence: 99%