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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

Endosialin expression in AJCC Stage III and IV Melanomas by IHC analysis Endosialin expression levels for PEAT AJCC Stage III and Stage IV melanoma specimens with MAb 9G5 IHC staining. Statistical analysis was assessed by Fisher’s exact test. NS, not significant
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Fig3: Endosialin expression in AJCC Stage III and IV Melanomas by IHC analysis Endosialin expression levels for PEAT AJCC Stage III and Stage IV melanoma specimens with MAb 9G5 IHC staining. Statistical analysis was assessed by Fisher’s exact test. NS, not significant

Mentions: All the PEAT melanoma specimens assessed for endosialin expression with IHC (18 stage III and 48 stage IV melanoma patients) were compared by stage. 78 % (n = 14) of stage III and 67 % (n = 32) of stage IV showed positive expression of endosialin (Fig. 2 and Table 3). There was no significant difference in the frequency of endosialin expression between stage III and IV metastatic melanomas in this cohort. This suggested that the expression of endosialin is not dependent on regional or distal disease status (Fig. 3).Fig. 2


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)

Endosialin expression in AJCC Stage III and IV Melanomas by IHC analysis Endosialin expression levels for PEAT AJCC Stage III and Stage IV melanoma specimens with MAb 9G5 IHC staining. Statistical analysis was assessed by Fisher’s exact test. NS, not significant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Endosialin expression in AJCC Stage III and IV Melanomas by IHC analysis Endosialin expression levels for PEAT AJCC Stage III and Stage IV melanoma specimens with MAb 9G5 IHC staining. Statistical analysis was assessed by Fisher’s exact test. NS, not significant
Mentions: All the PEAT melanoma specimens assessed for endosialin expression with IHC (18 stage III and 48 stage IV melanoma patients) were compared by stage. 78 % (n = 14) of stage III and 67 % (n = 32) of stage IV showed positive expression of endosialin (Fig. 2 and Table 3). There was no significant difference in the frequency of endosialin expression between stage III and IV metastatic melanomas in this cohort. This suggested that the expression of endosialin is not dependent on regional or distal disease status (Fig. 3).Fig. 2

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