title: The biological and prognostic significance of angiotropism in uveal melanoma.
abstract: Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of an alternative metastatic pathway.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.16.
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.|Faculty of Medicine, University of Paris Réné Descartes, Paris, France.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Barnhill
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Ye
authors.affiliation: U830 Inserm Unit, Center for Research, Institut Curie, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Batistella
authors.affiliation: U830 Inserm Unit, Center for Research, Institut Curie, Paris, France.
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Department of Radiation Oncology, Institut Curie, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Dendale
authors.affiliation: U932 Inserm Unit, Center for Research, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.affiliation: Faculty of Medicine, University of Paris Réné Descartes, Paris, France.|Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lugassy