Thalidomide Reduces Vascular Endothelial Growth Factor Immunostaining in Canine Splenic Hemangiosarcoma.

ABSTRACT

Hemangiosarcomas (HSA) are common neoplasms of dogs that often metastasize and are typically fatal. Recently it was demonstrated that thalidomide extends the survival time of dogs with HSA, potentially due to thalidomide-induced inhibition of vascular endothelial growth factor (VEGF) production by the neoplastic cells. To investigate this, immunostaining was used to evaluate VEGF within HSA metastases that developed after thalidomide treatment. The immunostaining was then compared to VEGF immunostaining in primary tumors from the same dogs prior to treatment with thalidomide and in metastatic tumors from untreated dogs with splenic HSA. Immunostaining was scored from 1 to 4 for each sample. Immunostaining in the metastatic lesions that had been treated with thalidomide had a mean immunostaining score of 1.4 which was significantly lower than the mean score in the corresponding primary splenic HSA (3.8, p = 0.02) and in metastases from untreated dogs (3.5, p = 0.02). This supports the hypothesis that thalidomide prolongs survival time in dogs with HSA due to inhibition of VEGF production by the neoplastic cells. As VEGF remained visible within HSAs exposed to thalidomide, additional treatments to inhibit VEGF production may further prolong survival times of dogs with these common canine neoplasms.