acid-phosphatase and Giant-Cell-Tumor-of-Bone

Serum tartrate-resistant acid phosphatase 5b is well known to be increased in giant cell tumors of bone. However, there are only a few studies that analyzed the association with tartrate-resistant acid phosphatase 5b expression in those patients. Therefore, we analyzed the characteristics of patients with giant cell tumors of bone and high tartrate-resistant acid phosphatase 5b expression.. This retrospective study included 26 patients with giant cell tumors of bone. The correlation between tartrate-resistant acid phosphatase 5b before initial treatment and tumor volume was evaluated. Patients were divided into two groups according to tartrate-resistant acid phosphatase 5b level. Statistical analysis was performed between the two groups.. Tartrate-resistant acid phosphatase 5b was elevated in 17/26 patients, and the mean value was 852 mU/dL. There was no correlation with tumor volume (r = 0.034, P = 0.86). The mean age of 34.5 years in the HT group was significantly younger than the mean age of 47.4 years in the LT group (P = 0.040). Pathologically, 19/26 cases showed at least one focal area with features of typical giant cell tumor of bone. Although 11/18 patients in the LT group exhibited relatively noticeable secondary changes, all patients in the HT group exhibited typical features (P = 0.0074).. Tartrate-resistant acid phosphatase 5b levels were not elevated in some giant cell tumors of bone. This study suggested that tartrate-resistant acid phosphatase 5b may be elevated in younger patients and in cases with fewer pathological secondary changes, regardless of tumor volume.

Topics: Acid Phosphatase; Adult; Biomarkers; Bone Neoplasms; Giant Cell Tumor of Bone; Humans; Middle Aged; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Tumor Burden

To investigate the serum levels of N-terminal telopeptide of type I collagen (NTx) and tartrate-resistant acid phosphatase 5b (TRACP5b) in giant cell tumor of bone (GCT) patients and the clinical implications.. 56 GCT patients (29 males and 27 females, 15 to 60 years old with a median age of 28.0 years old) with clinicopathological characteristics of GCT were enrolled in the Department of Bone Cancer, the Affiliated Cancer Hospital of Xinjiang Medical University from October 2008 to October 2014. The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of NTx and TRACP5b in the patients.. Compared with 21 patients who had a GCT of < 5 cm, the serum levels of NTx and TRACP5b in the 35 patients with a GCT of ≥ 5 cm were significantly increased (p < 0.05). Compared with those GCT patients who had a grade I tumor, the levels of NTx and TRACP5b in grade II patients were not increased (p > 0.05), but the levels of NTx and TRACP5b were significantly increased in grade III patients (p < 0.05). Moreover, compared with the patients in histologic stage I, the levels of NTx and TRACP5b in stage II GCT patients were not increased (p > 0.05), whereas the levels in grade III patients were significantly increased (p < 0.05). In addition, the location of the tumor had a significant effect on the serum levels of NTx and TRACP5b (p < 0.05).. Our study suggests that serum NTx and TRACP5b are sensitive and simple biomarkers to indicate aberrant bone metabolism in GCT patients, and they may have a clinical significance in GCT diagnosis. Combined examination for both markers helps in the classification of clinicopathological stages of GCT patients and in the prognosis of the disease.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers, Tumor; Bone Neoplasms; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Middle Aged; Neoplasm Grading; Peptides; Predictive Value of Tests; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed; Tumor Burden; Young Adult

Giant cell tumor of bone is an osteolytic, usually benign, tumor characterized by the infiltration of osteoclast-like giant cells. The receptor activator of nuclear factor kappa-B ligand pathway has been shown to play a key role in the pathogenesis of giant cell tumor. Treatment for refractory, recurrent, or metastatic giant cell tumor remains challenging. A monoclonal antibody to receptor activator of nuclear factor kappa-B ligand, denosumab, offers promise in these patients. Tartrate-resistant acid phosphatase 5b, a bone resorption marker, is secreted from osteoclasts and this marker is reported to be high in patients with giant cell tumor of bone. We investigated the effects of denosumab and the usefulness of a tartrate-resistant acid phosphatase 5b as a monitoring marker in the management of a refractory giant cell tumor of bone.. A 41-year-old Japanese male with right ischiac pain was diagnosed with a giant cell tumor in his right ischium. Since the tumor extended to the acetabulum, there was a possibility that en bloc resection might significantly impair function of the hip joint and curettage could cause massive bleeding. Therefore, denosumab therapy (120 mg, administered 3 times every 4 weeks) was performed before radical surgery. The giant cell tumor of bone was treated with denosumab successfully. No adverse reaction was noted. Tartrate-resistant acid phosphatase 5b secretion was measured in the patient's serum to monitor the response to denosumab, and a rapid normalization of the marker was observed after the first denosumab administration.. This case suggests that denosumab therapy might be an option for treating refractory giant cell tumor of bone, and that tartrate-resistant acid phosphatase 5b might be an early marker with which to monitor the efficacy of denosumab therapy for refractory giant cell tumor.

Topics: Acid Phosphatase; Adult; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Denosumab; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14+ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP+ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Giant Cell Tumor of Bone; Giant Cells; Growth Substances; Hepatocyte Growth Factor; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Membrane Proteins; Monocytes; Osteoclasts; Placenta Growth Factor; Pregnancy Proteins; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor D

The purpose of this study was to elucidate the clinical significance of acid phosphatase in giant cell tumour of bone.. Serum acid phosphatase levels were measured in 32 patients with this tumour both preoperatively and postoperatively.. Serum acid phosphatase value before surgery was high in 15 patients, whereas it was within normal limits in 17 patients. The serum acid phosphatase values of all the 15 patients with high preoperative serum level fell within normal limits postoperatively. In the remaining 17 patients in whom preoperative serum acid phosphatase values were within normal limits, postoperative serum acid phosphatase levels were lower than that of preoperative ones in all the patients. In addition, there was a statistically significant positive correlation between the tumour volume and the preoperative serum acid phosphatase level.. It is concluded that serum acid phosphatase is a useful tumour marker for giant cell tumour of bone.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged; Young Adult

Cherubism (CBM) and central giant cell granuloma (CGCG) of the jaw and giant cell tumor (GCT) of the long bone are clinically different diseases. Histologically, they are all multinucleated giant cell (MGC)-containing lesions. This study aims to evaluate the expression of c-Src and cytologic features in CBM, CGCG and GCT and to clarify whether there is a common mechanism underlying the formation of multi-nucleated giant cells (MGCs) in these lesions. Specimens and paraffin blocks were collected from patients with CBM (12 cases), CGCG (24 cases) and GCT (37 cases). Histomorpho-metric differences in MGCs were compared among the three types of lesions. The expression of c-Src by immunohistochemistry and in situ hybridization and the expression of TRAP by enzyme histochemical staining were examined. Expression of c-Src mRNA and protein, as well as TRAP staining, was detected in both MGCs and a fraction of mononuclear cells in all investigated lesions. There are no quantitative differences for cytologic features and c-Src expression among the lesions. The results suggested that CBM, CGCG and GCT have overlapping cytological features at the histological level, and c-Src may be involved in the formation of MGCs in the three different diseases.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Cherubism; Child; Gene Expression; Giant Cell Tumor of Bone; Giant Cells; Granuloma, Giant Cell; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Middle Aged; Proto-Oncogene Proteins pp60(c-src); Tartrate-Resistant Acid Phosphatase

Giant cell tumor of bone (GCT) is a bone-destroying tumor that sometimes recurs locally after treatment. A recent study showed increased levels of serum total acid phosphatase (TACP).. We assessed TACP in the serum of 26 patients with primary GCT, and in 5 of them who developed a local recurrence.. We found a correlation between TACP level in serum and tumor size. TACP levels that were elevated preoperatively in patients with GCT became normalized after surgery, but increased in 3 of the 5 patients with local recurrence.. TACP could be used as a tumor marker for monitoring response to treatment of GCT.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged; Neoplasm Recurrence, Local

Cathepsin K is a lysosomal cysteine proteinase (LCP) predominantly expressed in osteoclasts. This study was conducted to evaluate the importance of human cathepsin K for osteoclastic bone resorption relative to that of other LCPs. To accomplish this, we quantitatively determined the expression levels of major LCPs (cathepsins B, K, L, and S) in human osteoclastic cells by using competitive RT-PCR. Giant cell tumor of bone (GCT) was used as a source of human osteoclastic cells, since the tissue was shown to contain a large number of cells satisfying the criteria for typical osteoclasts. The involvement of LCPs in the bone-resorption process by the GCT cells was confirmed by showing that trans-epoxysucciny-L-leucylamido-(4-guanidino) butane (E-64), a nonselective cysteine proteinase inhibitor, exerted an inhibitory effect on the pit formation. We isolated osteoclast-like cells (OLCs) positive for tartrate-resistant acid phosphatase (TRAP) and cathepsin K from the GCT tissue to a degree of almost 95% purity. In these cells, the expression of cathepsin K was shown to be approximately 20-, 130-, and 410-fold stronger than that of cathepsins B, L, and S, respectively. A similar result was obtained when human bone marrow cells in culture were used as another source of OLCs. Further, we found that cathepsin K was expressed in OLCs far more strongly than in several human nonosteoclastic cells including osteoblastic cell lines. The abundant and selective expression of cathepsin K in OLCs relative to that of other LCPs suggests that cathepsin K is mainly responsible for osteoclastic degradation of human bone matrix.

Topics: Acid Phosphatase; Adult; Bone Marrow Cells; Bone Resorption; Calcitonin; Cathepsin K; Cathepsins; Cysteine Endopeptidases; DNA Primers; Dose-Response Relationship, Drug; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; Giant Cell Tumor of Bone; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Isoenzymes; Leucine; Osteoblasts; Osteoclasts; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

The serum acid phosphatase value was examined in nine patients with giant cell tumour of bone. Five showed a high level of acid phosphatase, which fell to within normal limits after surgery. Although the remaining four patients showed a normal acid phosphatase level before surgery, the postoperative acid phosphatase level was lower than the preoperative level in each case. Therefore, it is strongly suggested that serum acid phosphatase is a useful tumour marker in diagnosing giant cell tumour of bone as well as in evaluating the efficacy of treatment.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged

Spectrometry has been employed to assess the levels of collagenase, catepsin D, trypsin-like proteinases and their inhibitors as well as bone acid and alkaline phosphatase both in the center and along the periphery of giant cell tumor of bone (GCTB) and chondrosarcoma. The levels of collagenase, trypsin-like proteinases and their inhibitors in the center of chondrosarcoma were much higher while those of alkaline phosphatase--lower than along tumor periphery. The catepsin D and acid phosphatase concentrations of the center and periphery of chondrosarcoma were similar. It was suggested that an extremely low concentration of trypsin-like inhibitors may contribute to degradation of the matrix in tissues adjacent to chondrosarcoma and, consequently, to tumor invasion development.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Cathepsin D; Chondrosarcoma; Collagenases; Femoral Neoplasms; Femur; Giant Cell Tumor of Bone; Humans; Ilium; Statistics, Nonparametric; Tibia; Trypsin; Trypsin Inhibitors

The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta-E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts.

Topics: Acid Phosphatase; Adult; Base Sequence; Bone Neoplasms; Bone Resorption; Cathepsin B; Cathepsin D; DNA Primers; Estradiol; Female; Gene Expression; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Molecular Sequence Data; Osteoclasts; Receptors, Estrogen; RNA, Messenger; RNA, Neoplasm