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Updated: Aug 17, 2026
A Matrigel-Based Tube Formation Assay to Assess the Vasculogenic Activity of Tumor Cells
Published on: September 7, 2011
Distinguishing fibrovascular septa from vasculogenic mimicry patterns
Amy Y Lin1, Andrew J Maniotis, Klara Valyi-Nagy
1Department of Pathology, University of Illinois at Chicago, IL 60612, USA.
Context:
Molecular analyses indicate that periodic acid-Schiff (PAS)-positive (laminin-rich) patterns in melanomas are generated by invasive tumor cells by vasculogenic mimicry. Some observers, however, consider these patterns to be fibrovascular septa, generated by a stromal host response.
Objective:
To delineate differences between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas.
Design:
Frequency distributions, associations with outcome, and thicknesses of trichrome-positive and PAS-positive looping patterns were determined in 234 primary uveal melanomas. Sequential sections of 13 additional primary uveal melanomas that contained PAS-positive/trichrome-negative looping patterns were stained for type I and type IV collagens, laminin, and fibronectin. Real-time quantitative polymerase chain reaction was performed on RNA from cultured uveal melanoma cells for the expression of COL1A1, COL4A2, and fibronectin.
Results:
Trichrome-positive loops were encountered less frequently than PAS-positive loops (10% vs 56%, respectively). Death from metastatic melanoma was strongly associated with PAS-positive (P < .001) but not with trichrome-positive (P = .57) loops. Trichrome-positive loops were significantly thicker than PAS-positive loops (P < .001). The PAS-positive patterns stained positive for laminin, type I and type IV collagens, and fibronectin. Type I collagen was detected within melanoma cells and focally within some PAS-positive patterns. Real-time quantitative polymerase chain reaction revealed 3-fold, 25-fold, and 97-fold increases, respectively, in expression of COL4A2, fibronectin, and COL1A1 by invasive pattern-forming primary melanoma cells compared with poorly invasive non-pattern-forming cells.
Conclusions:
Fibrovascular septa are rare and prognostically insignificant in uveal melanomas, whereas vasculogenic mimicry patterns are associated with increased mortality. Type I collagen, seen focally in some vasculogenic mimicry patterns, may be synthesized by tumor cells, independent of a host stromal response.
Insights
Periodic acid-Schiff (PAS)-positive patterns in uveal melanoma indicate vasculogenic mimicry and are linked to increased mortality, unlike rare fibrovascular septa. Tumor cells may produce collagen, suggesting an intrinsic mechanism independent of stromal response.
Area of Science:
- Ophthalmology
- Oncology
- Pathology
Background:
- Periodic acid-Schiff (PAS)-positive patterns in melanomas are debated: some attribute them to tumor cell vasculogenic mimicry, while others suggest stromal fibrovascular septa.
- Distinguishing these patterns is crucial for understanding melanoma behavior and prognosis.
Purpose of the Study:
- To differentiate between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas.
- To assess the prognostic significance of these patterns.
Main Methods:
- Analysis of 234 primary uveal melanomas for trichrome-positive and PAS-positive looping patterns.
- Immunohistochemical staining for collagens, laminin, and fibronectin in sequential sections.
- Real-time quantitative polymerase chain reaction (PCR) for gene expression in melanoma cells.
Main Results:
- PAS-positive loops were more frequent (56%) than trichrome-positive loops (10%) and strongly associated with increased mortality.
- Trichrome-positive loops were thicker and not linked to outcome.
- PAS-positive patterns contained laminin, type IV collagen, and fibronectin; type I collagen was found in tumor cells and some PAS-positive areas.
- Uveal melanoma cells showed significantly higher expression of COL4A2, fibronectin, and COL1A1 compared to poorly invasive cells.
Conclusions:
- Fibrovascular septa are uncommon and prognostically irrelevant in uveal melanoma.
- Vasculogenic mimicry patterns, identified by PAS staining, correlate with higher mortality.
- Type I collagen in some mimicry patterns may originate from tumor cells, suggesting an autocrine or paracrine mechanism.
