Distinguishing Fibrovascular Septa From Vasculogenic Mimicry Patterns in Primary Uveal Melanoma

Abstract

Abstract: : Purpose: To delineate differences between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas. Methods: Frequency distributions, associations with outcome, and thicknesses of trichrome⁺ and PAS⁺ looping patterns were determined in 234 primary uveal melanomas. Tumors containing PAS⁺/trichrome^– looping patterns were stained for collagens 1 and 4, laminin and fibronectin. RQ–PCR was performed on RNA from cultured uveal melanoma cells for the expression of COL1A2, COL4A2, and fibronectin. Results: Trichrome⁺ loops were encountered less frequently than PAS⁺ loops (10% vs 56% respectively). Death from metastatic melanoma was strongly associated with PAS⁺ (p<0.0001) but not with trichrome⁺ loops (P=0.5702). Trichrome⁺ loops were significantly thicker than PAS–positive loops (P=0.0001). PAS⁺ patterns stained positive for laminin, collagens 1 and 4, and fibronectin. Collagen I was detected within melanoma cells and focally within some PAS⁺ patterns. RQ–PCR revealed a 3X, 25X, and 97X increase respectively in expression of collagen 4A2, fibronectin, and collagen 1A2 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 while vasculogenic mimicry patterns are associated with increased mortality. Collagen I, seen focally in some vasculogenic mimicry patterns, may be synthesized by tumor cells, independent of a host stromal response. Supported by NIH grant EY10457

Keywords: melanoma • pathology: human • microscopy: light/fluorescence/immunohistochemistry