Abstract
Canine osteosarcoma (OS) is an aggressive malignant bone tumor. Prognosis is primarily determined by clinical parameters. Vitamin D has been postulated as a novel therapeutic option for many malignancies. Upon activation, vitamin D receptors (VDRs) combine with retinoid receptor (RXR) forming a heterodimer initiating a cascade of events. Vitamin D's antineoplastic activity and its mechanism of action in OS remain to be clearly established. Expression of VDR, RXR, Ki-67, survivin, and ezrin was studied in 33 archived, canine OS specimens. VDR, RXR, survivin, and ezrin were expressed in the majority of cases. There was no statistically significant difference in VDR expression in relationship with tumor grade, type, or locations or animal breed, age, and/or sex. No significant association (p = 0.316) between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and VDR expression (ρ = −0.466), a positive correlation between survivin and RXR expression was found (p = 0.374). A significant relationship exists between VDR and RXR expression in OSs and proliferative/apoptosis markers. These results establish a foundation for elucidating mechanisms by which vitamin D induces antineoplastic activity in OS.
Highlights
Osteosarcoma (OS) is the most common primary bone tumor in dogs accounting for up to 85% of all primary malignant bone tumors [1, 2]
Vitamin D receptors (VDRs) combine with retinoid receptor (RXR) forming a heterodimer initiating a cascade of events
No significant association (p = 0.316) between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and vitamin D receptors (VDRs) expression (ρ = −0.466), a positive correlation between survivin and retinoid X receptors (RXR) expression was found (p = 0.374)
Summary
Osteosarcoma (OS) is the most common primary bone tumor in dogs accounting for up to 85% of all primary malignant bone tumors [1, 2]. Canine OS is a locally aggressive neoplasm and metastasis is extremely common [1]. While less than 15% of dogs have radiographic evidence of metastasis at the time of diagnosis and regional lymph node involvement is rare, approximately 90% of dogs diagnosed with OS would die of metastatic disease if amputation with clean margins was the only treatment [1]. The current standard of care consists of surgical excision with wide margins followed by chemotherapy for control of microscopic metastatic disease [1]. Radiation therapy has not been shown to be effective as a curative modality of treatment. It has primarily been used for palliative pain relief [3, 4]. Some have shown its value in downstaging a primary tumor prior to surgical excision [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
