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Endosialin Expression in Metastatic Melanoma Tumor Microenvironment Vasculature: Potential Therapeutic Implications.

Kiyohara E, Donovan N, Takeshima L, Huang S, Wilmott JS, Scolyer RA, Jones P, Somers EB, O'Shannessy DJ, Hoon DS - Cancer Microenviron (2015)

Bottom Line: There was no significant difference in endosialin and BRAFmt expression between stages III vs.IV specimens.Endosialin may be a potential therapeutic target by virtue of its selective expression in metastatic melanoma relative to normal tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Representative photos of endosialin expression in melanoma and normal tissues IHC was performed on normal liver, lung and metastatic melanoma tissues with MAb 9G5. Normal tissues revealed no endosialin expression. The vascular regions of metastatic melanoma showed strong endosialin expression. IgG: negative control staining with isotype Ab and endosialin: TEM-1 staining with MAb 9G5. Scale bar, 100 μm
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Fig1: Representative photos of endosialin expression in melanoma and normal tissues IHC was performed on normal liver, lung and metastatic melanoma tissues with MAb 9G5. Normal tissues revealed no endosialin expression. The vascular regions of metastatic melanoma showed strong endosialin expression. IgG: negative control staining with isotype Ab and endosialin: TEM-1 staining with MAb 9G5. Scale bar, 100 μm

Mentions: To evaluate the specificity and sensitivity of IHC methodology in detecting endosialin expression in the tumor microenvironment vasculature of metastatic melanoma using MAb 9G5, we compared endosialin expression in melanoma PEAT specimens with that of two normal tissue types (liver and lung) as controls (Fig. 1). Endosialin expression was significantly up-regulated within tumor vessels and stromal region of the melanoma specimens, while none was observed in the vascular regions of the normal controls. Moreover, as shown in a previous report, hepatocytes exhibited weak expression of endosialin, [20].Fig. 1


Endosialin Expression in Metastatic Melanoma Tumor Microenvironment Vasculature: Potential Therapeutic Implications.

Kiyohara E, Donovan N, Takeshima L, Huang S, Wilmott JS, Scolyer RA, Jones P, Somers EB, O'Shannessy DJ, Hoon DS - Cancer Microenviron (2015)

Representative photos of endosialin expression in melanoma and normal tissues IHC was performed on normal liver, lung and metastatic melanoma tissues with MAb 9G5. Normal tissues revealed no endosialin expression. The vascular regions of metastatic melanoma showed strong endosialin expression. IgG: negative control staining with isotype Ab and endosialin: TEM-1 staining with MAb 9G5. Scale bar, 100 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4542822&req=5

Fig1: Representative photos of endosialin expression in melanoma and normal tissues IHC was performed on normal liver, lung and metastatic melanoma tissues with MAb 9G5. Normal tissues revealed no endosialin expression. The vascular regions of metastatic melanoma showed strong endosialin expression. IgG: negative control staining with isotype Ab and endosialin: TEM-1 staining with MAb 9G5. Scale bar, 100 μm
Mentions: To evaluate the specificity and sensitivity of IHC methodology in detecting endosialin expression in the tumor microenvironment vasculature of metastatic melanoma using MAb 9G5, we compared endosialin expression in melanoma PEAT specimens with that of two normal tissue types (liver and lung) as controls (Fig. 1). Endosialin expression was significantly up-regulated within tumor vessels and stromal region of the melanoma specimens, while none was observed in the vascular regions of the normal controls. Moreover, as shown in a previous report, hepatocytes exhibited weak expression of endosialin, [20].Fig. 1

Bottom Line: There was no significant difference in endosialin and BRAFmt expression between stages III vs.IV specimens.Endosialin may be a potential therapeutic target by virtue of its selective expression in metastatic melanoma relative to normal tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA, USA.

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.

No MeSH data available.


Related in: MedlinePlus