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

Abstract

In a recent publication, Maniotis et al 1 report that blood vessels of malignant eye tumors known as uveal melanomas are formed by tumor cells instead of endothelial cells. The authors use the term vasculogenic mimicry to describe this phenomenon and consider it a novel concept in the biology of tumor vascularization. The paper has received widespread attention and apparent validation through two commentaries, one published along with the paper in The American Journal of Pathology 2 and another published concurrently in Science. 3 Despite the paper’s impact the evidence is, in our view, unconvincing. The problems are, however, not easily detected by readers unfamiliar with the background or pitfalls of this specialized topic. Although it is intriguing and worthy of further study, the evidence presented in Maniotis et al for a functionally significant contribution of tumor cell-lined blood vessels to vascularization and blood flow in uveal melanomas is neither persuasive nor novel. The purpose of this commentary is to examine the evidence for vasculogenic mimicry and the reasons for our assessment. (Note: This commentary does not address the in vitro or microarray data presented by Maniotis et al, because the interpretation of these results is dependent on the histological, immunohistochemical, and electron microscopic evidence that is the focus of our remarks. Also, this commentary does not question the validity of the relationship between the periodic acid-Schiff (PAS) staining pattern of uveal melanomas and clinical outcome, as reported by Folberg et al in several publications. 4,5 This correlation may be clinically useful even if the PAS staining pattern does not faithfully represent the microvascular architecture. Neither does our commentary question the usefulness of microvascular density as a prognostic factor for survival in uveal melanomas. 6,7 Indeed, PAS staining pattern and microvascular density may offer complementary indices of the lethality of these tumors. 6-9 )