Ovarian Low-grade Basaloid Carcinoma Arising in Brenner Tumor: A New Variant of Malignant Brenner Tumor.

Brenner tumors are uncommon ovarian neoplasms, most of which are benign, although borderline and malignant variants occur. We report 2 unusual ovarian neoplasms composed of an admixture of typical benign Brenner tumor and a low-grade epithelial neoplasm which we designate as low-grade basaloid carcinoma. The latter component morphologically and immunohistochemically resembled "salivary gland-type/myoepithelial" neoplasms with variable positive staining with cytokeratins, p63, S100, and CD117. One tumor exhibited aggressive behavior with local recurrence and distant metastasis. This neoplasm exhibited focal "high-grade" transformation with diffuse mutation-type p53 staining, in contrast to the wild-type immunoreactivity in the low-grade component. As far as we are aware, such neoplasms have not previously been reported in the literature and this represents a newly described morphologic variant of malignant Brenner tumor.

The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways.

Strontium ranelate exerts both an anti-catabolic and an anabolic effect on bone cells. To further investigate the molecular mechanism whereby strontium ranelate inhibits bone resorption, we focused our attention on the effects of strontium ranelate on osteoclast apoptosis and on the underlying mechanism(s). Using primary mature rabbit osteoclasts, we demonstrated that strontium (Sro2+) dose-dependently stimulates the apoptosis of mature osteoclasts. As shown previously for calcium (Cao2+), the Sro2+-induced effect on mature osteoclasts is mediated by the Cao2+-sensing receptor, CaR, which in turn stimulates a phospholipase C-dependent signaling pathway and nuclear translocation of NF-kappaB. Unlike Cao2+, however, Sro2+-induced osteoclast apoptosis was shown to depend on PKCbetaII activation and to be independent of inositol 1,4,5-trisphosphate action. As a consequence of these differences in their intracellular signaling pathways, Sro2+ and Cao2+ in combination were shown to exert a greater effect on mature osteoclast apoptosis than did either divalent cation by itself. Altogether, our results show that Sro2+ acts through the CaR and induces osteoclast apoptosis through a signaling pathway similar to but different in certain respects from that of Cao2+. This difference in the respective signaling cascades enables Sro2+ to potentiate Cao2+-induced osteoclast apoptosis and vice versa. In this manner, it is conceivable that Sro2+ and Cao2+ act together to inhibit bone resorption in strontium ranelate-treated patients.