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Distinguishing Fibrovascular Septa From Vasculogenic Mimicry Patterns

2005; American Medical Association; Volume: 129; Issue: 7 Linguagem: Inglês

10.5858/2005-129-884-dfsfvm

1543-2165

Amy Lin, Andrew J. Maniotis, Klara Valyi‐Nagy, Dibyen Majumdar, Suman Setty, Shri Hari Kadkol, Lu Leach, Jacob Pe’er, Robert Folberg,

Ocular Oncology and Treatments

Abstract 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.