Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas.

Overexpression of the ubiquitous protein kinase, CK2α, has been reported in various human cancers. Here, we demonstrate that nuclear and nucleolar CK2α localization in invasive ductal carcinomas of the breast is a reliable predictor of poor prognosis. Cellular localization of CK2α in nuclei and nucleoli was analyzed immunohistochemically using surgical tissue blocks from 112 patients, who had undergone surgery without neoadjuvant chemotherapy. Clinical data collection and median follow-up period were for more than 5 y. In total, 93.8% of patients demonstrated elevated CK2α expression in nuclei and 36.6% of them displayed elevated expression predominantly in nucleoli. Clinicopathological malignancy was strongly correlated with elevated nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly worse (P = .0002) in patients with positive nucleolar CK2α staining. The 5-y survival rate decreased to a roughly 50% in nucleolar CK2α-positive patients of triple-negative (P = .0069) and p Stage 3 (P = .0073) groups. In contrast, no patients relapsed or died in the triple-negative group who exhibited a lack of nucleolar CK2α staining. Evaluation of nucleolar CK2α staining showed a high secondary index with a hazard ratio of 6.629 (P = .001), following lymph node metastasis with a hazard ratio of 14.30 (P = .0008). Multivariate analysis demonstrated that nucleolar CK2α is an independent factor for recurrence-free survival. Therefore, we propose that histochemical evaluation of nucleolar CK2α-positive staining may be a new and robust prognostic indicator for patients who need further treatment. Functional consequences of nucleolar CK2 dysfunction may be a starting point to facilitate development of novel treatments for invasive breast carcinoma.

Evaluation of a Newly Designed Microperforated Titanium Membrane with Beta-Tricalcium Phosphate for Guided Bone Regeneration in Dog Mandibles.

PURPOSE: This study evaluated the efficacy of newly designed, laser-perforated pure titanium membranes for guided bone regeneration using beta-tricalcium phosphate (ß-TCP), and compared them with the existing membrane. MATERIALS AND METHODS: Bilateral acute lateral ridge defects were created in the mandibles of 12 dogs (four defects per animal), which were then randomly divided into two groups (six dogs each). The twenty-four bone defects in each group were then further divided into five groups. The groups were as follows: (1) F001M0, a prototype membrane without a frame plus ß-TCP (n = 5); (2) F001M1, a prototype membrane with a frame plus ß-TCP (n = 5); (3) FBS, an existing control membrane plus ß-TCP (n = 5); (4) control 1, ß-TCP without membrane and with covering flap only (n = 5); and (5) control 2, no treatment (no ß-TCP and no membrane) (n = 4). In all groups where ß-TCP was used, it was mixed with peripheral blood. The animals were necropsied at 6 or 12 weeks postoperatively (six dogs each), and samples were collected and processed for radiographic, histologic, and histomorphometric analyses. RESULTS: Among the three membrane groups, regenerated tissue and bone volume was greatest in the F001M1 group at both 6 and 12 weeks postoperatively, although differences among groups were not statistically significant. Bone mineral density was similar among the membrane groups. Histologic analysis revealed that immature fibroblasts were present on the laser-perforated portion at 6 weeks, which induced vascularization. In addition, more calcified bone was replaced beneath the prototypes than beneath the FBS membrane at 12 weeks. Histomorphometric analyses revealed that the calcific osseous areas at 12 weeks after surgery were significantly greater in the F001M1 and F001M0 groups than in the FBS group (P = .021, P = .032). Furthermore, the fibrous tissue areas beneath the membrane at 12 weeks postoperatively were significantly smaller in the prototype groups than in the FBS group (P = .02, P = .02). CONCLUSION: The efficacies of both prototype membranes were not inferior to that of the FBS membrane, indicating that they may facilitate bone regeneration and maturation when ß-TCP mixed with autologous blood is employed.