Distinguishing fibrovascular septa from vasculogenic mimicry patterns.
BACKGROUND
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.


METHODS
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.
Lin
Amy Y
AY
Department of Pathology, University of Illinois at Chicago, IL 60612, USA.
Maniotis
Andrew J
AJ
Valyi-Nagy
Klara
K
Majumdar
Dibyen
D
Setty
Suman
S
Kadkol
ShriHari
S
Leach
Lu
L
Pe'er
Jacob
J
Folberg
Robert
R
D001391:Azo Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D002830:Choroid Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002924:Ciliary Body / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000737:chemistry / Q000235:genetics; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007797:Laminin / Q000378:metabolism; D008545:Melanoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D018716:Molecular Mimicry / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D010503:Periodic Acid-Schiff Reaction / Q000379:methods*; D017510:Protein Folding; D014604:Uveal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology
D001391:Azo Compounds; D024042:Collagen Type I; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D009363:Neoplasm Proteins; C042643:Martius scarlet blue trichrome