title: Endosialin Expression in Metastatic Melanoma Tumor Microenvironment Vasculature: Potential Therapeutic Implications.
abstract: Ontuxizumab (MORAb-004) is a humanized recombinant antibody targeting endosialin (TEM-1, CD248). We conducted an analysis of endosialin expression in metastatic melanoma specimens using the anti-endosialin rat anti- MAb 9G5, in order to determine the potential of endosialin as a therapeutic target within the tumor microenvironment vasculature. Endosialin expression in paraffin-embedded archival tissue block (PEAT) melanoma tissues was assessed using immunohistochemistry (IHC) with the anti-endosialin, MAb 9G5, in the vessels of American Joint Commission on Cancer (AJCC) Stage III (n = 18) and Stage IV (n = 48) specimens. IHC for endosialin expression was further performed on a TMA that included 136 Stage IV and 33 paired Stage III melanoma specimens. BRAF mutation (mt) was also evaluated in individual melanoma specimens and as well as the TMA. Analysis showed 70 % of melanoma specimens (n = 46) were positive for endosialin expression. There was no significant difference in endosialin and BRAFmt expression between stages III vs. IV specimens. Endosialin expression was detected in 86 % (n = 117) of stage IV TMA specimens, while no expression was detected in 29 normal tissue controls. MAb 9G5 detects the presence of endosialin in the microenvironment tumor vasculature of most metastatic melanoma tissues, regardless of clinical stage and presence of BRAFmt. Endosialin may be a potential therapeutic target by virtue of its selective expression in metastatic melanoma relative to normal tissues.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kiyohara
authors.forename: Nicholas
authors.initials: N
authors.lastname: Donovan
authors.forename: Ling
authors.initials: L
authors.lastname: Takeshima
authors.forename: Sharon
authors.initials: S
authors.lastname: Huang
authors.forename: James S
authors.initials: JS
authors.lastname: Wilmott
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Somers
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: O'Shannessy
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon