Clinicopathologic correlation of vitamin D receptor expression with retinoid X receptor and MIB-1 expression in primary and metastatic osteosarcoma. Vitamin D, in addition to its effects on bone, is important in cell cycle regulation. Vitamin D receptor (VDR) has been identified in breast, prostate, and colon cancers, as well as in canine and human osteosarcoma (OS) cell lines; however, it has not been well investigated in human OS-archived specimens. We correlated VDR, retinoid X receptor (RXR), and MIB-1 (Ki-67) expression in 110 archived OS cases with several clinicopathologic parameters including patient's age, sex, tumor location, tumor grade, and type and metastatic status. The expression of VDR and RXR was identified in human OS tissue obtained from primary and metastatic OS archival tissue. No statistically significant difference was found in VDR expression in relation with tumor grade, type, age, sex, or location. The expression of RXR was highest in higher-grade (P = .0006) and metastatic tumors but remained unchanged when correlated with tumor type, age, sex, or location. The expression of MIB-1 was statistically elevated in higher-grade tumors (P = .001), patients 25 years or younger (P = .04), tumors located in extremities (P = .005), and metastatic lesions, but was not impacted by tumor type or patient's sex. Proliferative activity was significantly reduced after treatment, as the mean MIB-1 expression dropped from 11% in primary biopsy samples to 6% in resection specimens. There appears to be a relationship between proliferative tumor activity and tumor grade, location, and metastasis. Additional studies on the analysis of the effects of vitamin D and RXR on OS proliferation, apoptosis, and differentiation are critical to further evaluate their potential role in OS treatment.Copyright © 2012 Elsevier Inc. All rights reserved.