Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors and therefore constitutes a potential target of therapy. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) (Bevacizumab, Avastin, Roche) or their receptors (Thyrosine Kinase Inhibitors, TKI) have been approved by FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied. To ascertain the presence of potential therapeutic targets, we have analysed by immunohistochemistry the expression of VEGF A, VEGF C, VEGF D, and of their TK receptors R1, R2, and R3 in Thymic Epithelial Tumors (TET). Platelet Derived Growth Factor Receptorβ (PDGFRβ) was also included in this list because is another pro-angiogenic TK receptor that can be inhibited by available TKI (eg: Sorafenib, Sunitinib). Methodologically, we have arranged in Tissue Micro Arrays (TMA) duplicate samples from 200 primary TET, collected for a retrospective study sponsored by the Italy-US program ( US- and Italian-NIH ) for Rare Diseases. This series comprised 53 cases (26.5%) “benign” histotypes (A, AB, Micronodular Thymoma-MNT), 31 cases (15.5%) B1 low-malignant TET, 100 cases (50%) B2/B3 TET (intermediate malignancy) and 16 (8%) Thymic carcinoma (Ca). To evaluate the reactivity of Avastin, tumor sections were stained with this antibody after biotinylation. The coexpression in epithelial cells of growth factors and their receptors suggests the presence of autocrine mechanisms in TET. According to preliminary data, in relapsing/metastatizing tumors, marker expression’s pattern changes during progression. TET express potential targets (to be validated as predictive) of anti-angiogenesis drugs. The comparative low reactivity of the therapeutic antibody Avastin when compared to anti-VEGF A antibodies is another example underlying the need for the standardization of target assessment in terms of reagents and procedures
Expression of angiogenesis-related biomarkers in thymic epithelial tumors (TET).
PALESTRO, Giorgio;CHIARLE, Roberto;PICH, Achille;
2010-01-01
Abstract
Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors and therefore constitutes a potential target of therapy. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) (Bevacizumab, Avastin, Roche) or their receptors (Thyrosine Kinase Inhibitors, TKI) have been approved by FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied. To ascertain the presence of potential therapeutic targets, we have analysed by immunohistochemistry the expression of VEGF A, VEGF C, VEGF D, and of their TK receptors R1, R2, and R3 in Thymic Epithelial Tumors (TET). Platelet Derived Growth Factor Receptorβ (PDGFRβ) was also included in this list because is another pro-angiogenic TK receptor that can be inhibited by available TKI (eg: Sorafenib, Sunitinib). Methodologically, we have arranged in Tissue Micro Arrays (TMA) duplicate samples from 200 primary TET, collected for a retrospective study sponsored by the Italy-US program ( US- and Italian-NIH ) for Rare Diseases. This series comprised 53 cases (26.5%) “benign” histotypes (A, AB, Micronodular Thymoma-MNT), 31 cases (15.5%) B1 low-malignant TET, 100 cases (50%) B2/B3 TET (intermediate malignancy) and 16 (8%) Thymic carcinoma (Ca). To evaluate the reactivity of Avastin, tumor sections were stained with this antibody after biotinylation. The coexpression in epithelial cells of growth factors and their receptors suggests the presence of autocrine mechanisms in TET. According to preliminary data, in relapsing/metastatizing tumors, marker expression’s pattern changes during progression. TET express potential targets (to be validated as predictive) of anti-angiogenesis drugs. The comparative low reactivity of the therapeutic antibody Avastin when compared to anti-VEGF A antibodies is another example underlying the need for the standardization of target assessment in terms of reagents and procedures
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