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PubMedDate not supplied

Osteosarcoma cells in tissue culture: II. Characterization and localization of alkaline phosphatase activity.

Although elevated alkaline phosphatase levels in osteosarcoma have been shown to be related to prognosis, the functional significance is unclear. Human osteosarcoma cells in tissue culture retain detectable amounts of alkaline phosphatase activity. In this study the specific activity of that enzyme was compared in 13 osteosarcoma tissue culture lines and 13 normal skin fibroblast lines derived from the same patients. Osteosarcoma cells had significantly higher baseline alkaline phosphatase levels and could be stimulated with hydrocortisone to produce more enzymatic activity than the fibroblast lines. Activity was localized ultracytochemically to the cell membrane and to many small intracellular vesicles in stimulated osteosarcoma cells. These observations aid in the differentiation of osteosarcoma and fibroblast lines in tissue culture and suggest an association between elevated alkaline phosphatase levels and metabolic abnormalities in patients with osteosarcoma.

Acid Phosphatase↗
PubMed1981

Isolation of tumor cells from patients with osteosarcoma and analysis of their sensitivity to methotrexate.

Many clinical studies have been conducted on the role of high-dose methotrexate (MTX) in human osteosarcoma, but information about the in vitro effect of MTX on human osteosarcoma cells is lacking. In this paper, the effect of MTX on tumor cells derived from seven patients with osteosarcoma has been studied in an attempt to correlate clinical and in vitro sensitivity to the drug. Isolation of the cells from the primary tumors (four patients) or metastasis (three patients) was carried out with a collagenase treatment followed by purification through a density gradient. The osteosarcoma cells were identified by electron microscopy and histochemical reactions. The cellular sensitivity to MTX was measured by the inhibitory effect of MTX on [3H]deoxyuridine incorporation into DNA. This incorporation ws 50% inhibited in primary tumors at concentrations from 3 X 10(-7) to 3 X 10(-6) M. The metastatic cells isolated from patients that were clinically resistant to high-dose MTX had a 50% inhibition ranging from 1.5 X 10(-7) to 4 X 10(-5) M. Human stimulated lymphocytes, Sarcoma 180 cells, and Ehrlich ascitic mouse cells had a 50% inhibition of about 1.5 X 10(-7) M. When [3H]thymidine incorporation into DNA of human osteosarcoma cells was studied, it was observed that MTX increased its incorporation up to 4-fold. This increase was stable for at lest 6 hr and was only slightly enhanced by the addition of hypoxanthine. The stimulation by MTX of [3H]thymidine incorporation into DNA in stimulated lymphocytes and Ehrlich cells is much smaller, between 40 and 60%. A hypothesis to explain these results is that osteosarcoma cells build their deoxythymidine monophosphate pool largely through the de novo pathway, the salvage pathway being less important. It is suggested that the importance of the de novo pathway for deoxythymidine monophosphate synthesis is a biochemical characteristic of the osteosarcoma cells which could be related to the initial sensitivity of this tumor to MTX and that an activation of the salvage pathway could constitute an additional mechanism of resistance to this drug.

Cell Separation↗
PubMed1995

Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide.

The successful treatment of metastases will have to include modalities that can overcome the obstacles presented by the heterogeneous nature of malignant neoplasms and the continuous evolution of variant cells. Macrophages activated to become tumoricidal by interaction with L-MTP-PE may be able to accomplish this. Osteosarcoma appears to be an ideal disease in which to employ L-MTP-PE as an additional adjuvant to present chemotherapy regimens. The lung is the most frequent site of metastases, and pulmonary micrometastases are considered to be present in the majority of patients at diagnosis. Approximately 40% of patients with osteosarcoma develop pulmonary metastases despite the administration of adjuvant chemotherapy. The 2-year disease-free interval has not improved over the past 10 years, despite multiple changes in adjuvant regimens. These data argue that there is a subpopulation of patients who harbor tumor cells that are relatively resistant to all chemotherapy. Unfortunately, this group of patients cannot be identified at the time of initial diagnosis. This necessitates the incorporation of new forms of therapy into the adjuvant chemotherapy protocols for all patients in the hope of eradicating the resistant cells harbored in the 40%. Based on the data summarized previously, L-MTP-PE may improve the clinical outcome of patients with osteosarcoma by activating pulmonary macrophages to destroy residual tumor cells that are not eliminated by chemotherapy. Monocytes from osteosarcoma patients can be rendered cytotoxic to tumor cells by in-vitro incubation with L-MTP-PE and following the intravenous administration of this agent. L-MTP-PE can be given safely to both adults and children with minimal side effects. The whole-body distribution of 99mTc-labeled liposomes containing MTP-PE confirms that the agent is taken up by the lungs. Biologic activity in osteosarcoma patients is revealed by the elevations in plasma levels of several cytokines plus stimulation of monocyte-mediated cytotoxicity following L-MTP-PE infusion and by histologic changes in the pulmonary lesions. Ifosfamide therapy given in combination with L-MTP-PE does not suppress this immune response, as judged by both plasma cytokine levels and tumor histology. Finally, L-MTP-PE has been shown to be effective as a single agent against relapsed osteosarcoma. It is unlikely that the addition of other chemotherapeutic agents to the adjuvant chemotherapy protocols will alter the 65% to 70% 2-year disease-free survival rate associated with osteosarcoma. The preceding data indicate that L-MTP-PE is an active agent against this disease and deserves further investigation. Therefore, the inclusion of L-MTP-PE with chemotherapy is a reasonable alternative to consider to improve the response rate of this disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Role of platelet membrane glycoproteins Ib/IX and IIb/IIIa, and of platelet alpha-granule proteins in platelet aggregation induced by human osteosarcoma cells.

We have previously shown that the platelet-aggregating activity of human MG-63 and HOS osteosarcoma cells depends at least in part upon tumor cell surface-associated thrombospondin, and suggested that platelet-osteosarcoma cell interactions could occur through interactions with specific platelet membrane receptors. In this study, the platelet-aggregating activity of MG-63 and HOS cells was studied by using a variety of platelet disorders. Both osteosarcoma cell lines induced a biphasic platelet aggregation response when added to normal platelet-rich plasma, while the second phase of aggregation was absent when added to gray platelets (deficiency in alpha-granule proteins) and to aspirin-treated platelets. Platelets from two unrelated patients with type I Glanzmann's thrombasthenia (deficiency in glycoprotein (GP) GPIIb/IIIa) did not aggregate at all with osteosarcoma cells. Using giant platelets from three patients with Bernard-Soulier syndrome (deficiency in GPIb/IX), the aggregation response induced by MG-63 and HOS cells was monophasic and reversible when compared to normal-sized platelets and to giant platelets from a patient with May-Hegglin anomaly (no membrane GP defect). Because GPIb serves as a receptor for von Willebrand factor during hemostasis, aggregation experiments were also conducted with the platelet-rich plasma of two patients with a low plasma von Willebrand factor concentration (type I von Willebrand's disease) before and after the infusion of deamino-D-arginine vasopressin. MG-63 and HOS cells induced biphasic platelet aggregation both before and after deamino-D-arginine vasopressin treatment, while the ristocetin-dependent binding of von Willebrand factor to platelets only occurred after deamino-D-arginine vasopressin treatment. Preincubation of normal platelet-rich plasma with monoclonal antibody SZ-2 directed against the von Willebrand binding domain of GPIb did not inhibit the platelet-aggregation activity of osteosarcoma cells, whereas anti-GPIb antibody SZ-2 did inhibit ristocetin-induced platelet agglutination. In addition, anti-GPIX antibodies did not affect platelet-osteosarcoma cell interactions. In conclusion, our data demonstrate that the first phase of the platelet-aggregating activity of human osteosarcoma cells is initiated by the interaction of these tumor cells with platelet membrane GPIIb/IIIa, whereas the second phase, even if plasma von Willebrand factor is deficient, involves platelet membrane GPIb and the participation of platelet alpha-granule proteins in membrane-mediated events, making aggregation irreversible.

Antibodies, Monoclonal↗
PubMed1993

Sporadic amplification of the MYC gene in human osteosarcomas.

The MYC proto-oncogene has been shown to be overexpressed in several types of sarcomas, including some osteosarcomas. In most cases, the overexpression is due to gene amplification. The total number of osteosarcoma patients studied, however, remains too small to derive any conclusions regarding the true prevalence and the possible clinical significance of MYC gene amplification. To address the issue more thoroughly, we studied 27 specimens from 25 patients with high-grade osteosarcoma (16 primary, 11 metastatic; 11 adult, 14 pediatric) for MYC gene alterations by Southern blot analysis. Two of 27 specimens (7%) showed MYC gene amplification: a primary fibrohistiocytic osteosarcoma of the femur in a 37-year-old man showed threefold amplification, and a primary Paget's osteosarcoma of the tibia in a 60-year-old man showed fourfold amplification. None of the specimens tested showed MYC gene rearrangement (zero of 27) or activating point mutations at the PvuII site in MYC exon-1 (zero of 26). Hence, the MYC gene is amplified in a subset of osteosarcomas. The possible clinical or biological significance of MYC gene amplification in osteosarcoma may warrant further investigation.

Adult↗
PubMed1993

Osteoblastoma-like osteosarcoma. The Rizzoli Institute experience.

A series of 11 osteosarcomas that histologically resembles osteoblastoma was reviewed. The ages of the seven males and four females ranged from 19 to 47 yr (average 29). In six patients the roentgenograms showed cortical destruction and poorly defined borders on the lesion; this roentgenographic presentation was suggestive of malignancy. Histologically, the tumor permeation of the surrounding host tissue allowed us to differentiate osteoblastoma-like osteosarcoma from osteoblastoma. The differential diagnosis can be very difficult or even impossible on a small biopsy. The first diagnosis was considered benign in nine of our cases. Osteoblastoma-like osteosarcoma is a rare variety of osteosarcoma (1.1% of all osteosarcoma). It is a low-grade malignant lesion in which recurrence is the rule when adequate surgical margins were not achieved (five patients). Two of these patients died from tumors after inadequate surgical treatment of the primary tumor as well as of the recurrences. The six patients who were treated with wide surgical margins were alive without recurrence. One of them had lung metastasis, twice, treated with wide-wedge resection. Osteoblastoma-like osteosarcoma is a low-grade variety of osteosarcoma with characteristic histopathologic features. It needs to be recognized by the pathologist to achieve the right treatment which is wide surgical procedure.

Adult↗
PubMed1997

[Primary spinal osteosarcomas].

The rarity of primary osteosarcoma of the spine led us to index the 66 reported cases published in literature. From this analysis a difference was found between spinal osteosarcoma and osteosarcoma of the extremities. Tumors of the spine appear to be two times more frequent in the male population in their thirties. The average period between the beginning of the symptoms and the first consultation is seven months. Back pain is permanent and localized to the affected vertebra. In 80 percent of the cases, neurological symptoms already exist at the stage of the diagnosis. Magnetic resonance imaging (MRI), computed tomography and standard X-ray remain complementary in the morphological analysis of this tumor. All the aspects from the lytic to sclerotic forms are noted, although the lytic form is common. Among spinal osteosarcoma, the lumbar vertebrae are the most frequently affected. Diagnosis can only be established by pathology, even though this may also lead to some errors. In all the reported cases surgery is used, but carcinological methodology is not possible and a complete removal of affected tissue is difficult, with this being achieved in only a quarter of the cases. Radiation therapy, when used, requires doses of 70 Gy to 80 Gy without any certitude of controlling the tumour and with high risks of post-radiation complications. Chemotherapy on its own, despite the use of high-dose methotrexate, only has a temporary effect due to partial action on the primary center. Twenty years ago, only twenty percent of all patients suffering from osteosarcoma lived beyond two years, with worse prognosis for spinal osteogenic sarcoma. Today, the therapeutic approach for spinal tumors uses techniques developed in the treatment of osteosarcoma of the extremities, which can now expect more than seventy percent of all patients to live beyond five years. Present day methods recommend a rapid confirmation of the diagnosis, and then a neoadjuvant chemotherapy followed by surgery to remove all the affected area. This strategy allows an evaluation of the tumor chemosensitivity and to adapt the treatment in consequence. The latest results of this treatment on spinal osteosarcoma appear to be encouraging.

Humans↗
PubMedDate not supplied

Status of the p53, Rb and MDM2 genes in canine osteosarcoma.

The key role of p53 and Rb alterations in human osteosarcoma is clear. For example, osteosarcoma is common in individuals inheriting mutant p53 or Rb genes. Osteosarcoma in dogs is similar to humans by histology, site, gender ratio and several other biological parameters. To study whether this similarity extends to the molecular level, 21 canine osteosarcomas were analyzed for alterations of p53, Rb and MDM2. MDM2 is a normal cell protein which antagonizes p53, amplification is seen in some human sarcomas. The gross structure of the p53, Rb and MDM2 genes was examined by Southern blotting. No deletions or rearrangements of the p53 or Rb genes were detected. The absence of gross gene alterations affecting these tumor suppressor genes is a significant difference between the disease in dogs and humans, since rearrangements or deletions of the p53 or Rb genes occur in 20-30 per cent of human osteosarcomas. The MDM2 gene appeared to be duplicated in one canine tumor but no cases of significant amplification were detected. Expression of normal Rb was detected in all cases. Mutations of the p53 gene were found in 38 percent of canine osteosarcomas. Analysis of mutations revealed a predominance of spontaneous mutation. These finding emphasize the key role that alterations of p53 have in the development of osteosarcoma in dogs and humans.

Animals↗
PubMed1998

Osteosarcoma of the larynx.

Malignant mesenchymal tumors of the larynx constitute 0.3% to 1% of all laryngeal cancers, and of these osteosarcoma is the rarest. Our review of the literature identified only 12 cases of osteosarcoma of the larynx, all of which occurred in men. Rarely, osteosarcoma of the larynx may follow radiation therapy for squamous cell carcinoma, or the larynx may be the site of metastatic osteosarcoma. We report a case of primary laryngeal osteosarcoma arising in the cricoid cartilage and the first case of osteosarcoma of the larynx occurring in a woman.

Cricoid Cartilage↗
PubMed1997

Small cell osteosarcoma of bone. Review of 72 cases.

BACKGROUND: Small cell osteosarcoma of bone is a rare form of osteosarcoma, with an incidence rate of 1.3%. This tumor must be differentiated from other small cell malignancies because of treatment considerations, particularly patient response to chemotherapy. METHODS: Clinicopathologic findings in 72 cases (22 from Mayo Clinic files and 50 from consultation files) of small cell osteosarcoma of bone were studied. RESULTS: The femur was the most common bone involved, although the tumor was found in all portions of the skeleton. Radiographic features (available in 35 cases) suggested a diagnosis of osteosarcoma in 20 cases, Ewing's sarcoma or lymphoma in 14 cases, and giant cell tumor in 1 case. Histologically, there were four types according to the predominant cell size and cytologic features. Osteoid production was identified in all tumors. Complete treatment and follow-up data were available for 45 cases. Generally, in those cases without surgical treatment, greater than 60% of patients died of disease within 2 years. If the surgical procedure was associated with a marginal tumor margin, the prognosis was poor. In the 30 patients with wide or radical surgical margins, at last follow-up 13 were alive with no evidence of disease, 2 were alive with disease, and 15 died of disease at 5 months to 13.1 years after diagnosis. In 16 of 22 Mayo Clinic patients, excluding those who presented with metastasis, the cumulative 5-year survival rate was 28.9%. Median survival time in patients who had surgery with additional chemotherapy was 13.4 years, compared with 1.4 years in patients who underwent surgery alone (P = 0.17). CONCLUSIONS: Small cell osteosarcoma is a definite reproducible histologic entity. Treatment should be based on a protocol for osteosarcoma.

Adolescent↗
PubMed2000

Osteosarcomas of flat bones in adolescents and adults.

BACKGROUND: Osteosarcomas typically are long bone tumors and rarely affect the flat bones of the axial or appendicular skeleton. METHODS: The authors examined cases of high grade osteosarcoma of flat bones diagnosed at La Timone Adults University Hospital during a 16-year period. RESULTS: Sixteen patients with flat bone osteosarcomas were treated between 1980-1997. The median age of the patients was 25 years, with a male-to-female ratio of 14:2. Common presenting symptoms were swelling, pain, or both. Primary therapy included resection (n = 11 patients: alone in 8 patients and with radiation therapy in 3 patients), radiation therapy (n = 2 patients), or no local treatment (n = 3 patients). All patients received polychemotherapy, 7 preoperatively and postoperatively and 9 in the adjuvant setting. The overall 5-year survival rate was 47.7%; the overall median survival was 39 months (range, 4-211 months). The adequate local control rate was 68.7%. The local recurrence rate in patients who benefited from local treatment was 54%. Significant adverse prognostic factors on survival included the presence of synchronous metastases (three patients), metastases at any time during the course of the disease (eight patients), and inadequate local control (five patients). The overriding predictor of survival appeared to be the presence of metastases. Local recurrence appeared to have no influence on survival. No patient with metastases was alive at 3 years, whereas patients without recurrence or with local recurrence alone had a 5-year survival rate of 100%. Because the majority of patients with flat bone osteosarcomas ultimately die of metastatic disease, intensive systematic polychemotherapy should be an important component of treating these tumors. CONCLUSIONS: Based on the very encouraging results observed in the treatment of long bone osteosarcomas, the therapy for flat bone osteosarcomas should combine radical surgery with preoperative and postoperative adjuvant chemotherapy.

Adolescent↗
PubMed1998

Expression of the smooth muscle calponin gene in human osteosarcoma and its possible association with prognosis.

The basic calponin gene is a smooth muscle differentiation-specific gene that encodes an actin-binding protein involved in the regulation of smooth muscle contractility. We studied the expression of the calponin gene in 8 human osteosarcoma cell lines and 17 primary human osteosarcoma tissues by RT-PCR analysis. We also analyzed mRNA expression of smooth muscle-specific genes including SM22alpha, caldesmon and alpha-actin, and for neutral and acidic calponin isoforms. The genes were expressed at various levels by osteosarcoma cell lines and tissues of diverse histological subtypes. The basic calponin protein of an expected size was detected in osteosarcoma cell lines by immunoblot analysis and was localized by immunohistochemistry in the cytoplasm of the tumor cells in osteosarcoma tissues. Survival was found to be significantly increased in patients whose tumors exhibited basic calponin expression, compared with those with no expression. Alterations in the expression of other markers examined were not correlated with prognosis. Our results suggest that the basic calponin gene product may be a novel prognostic variable in patients with osteosarcoma.

Adolescent↗
PubMed1996

Cytogenetic studies on fine-needle aspiration samples from osteosarcoma and Ewing's sarcoma.

The preoperative multidrug chemotherapy of osteosarcoma and Ewing's sarcoma patients requires a reliable diagnosis. There are several advantages with obtaining the diagnosis by fine-needle aspiration (FNA) and cytologic examination. Although cytologic criteria have been defined, adjunctive methods such as cytogenetic analysis are valuable to support the diagnosis. We have cytogenetically analyzed FNAs from 18 primary bone sarcomas (six osteosarcomas and 12 Ewing's sarcomas). Two of the osteosarcomas showed abnormal, complex karyotypes seen in most highly-malignant osteosarcomas. Seven Ewing's sarcoma aspirates displayed abnormal karyotypes; five of these had the characteristic 11;22 translocation, and in one of these cases molecular genetic analysis revealed the hybrid EWS/FLI1 transcript. Since only two of six osteosarcomas showed clonal changes, chromosomal analysis of FNAs from suspected osteosarcoma seems to be of limited value, but may in some cases support the diagnosis of high-grade malignancy. In Ewing's sarcomas, however, the finding of an 11;22 translocation was valuable and strongly supported the cytologic diagnosis. As shown in one case, the material obtained by FNA is sufficient for cytologic, cytogenetic, and molecular genetic analysis.

Adolescent↗
PubMed1982

Cellular DNA content in human osteosarcoma: aspects on diagnosis and prognosis.

The cellular DNA content was determined in a consecutive series of 26 classical and two paraosteal osteosarcomas by means of single cell cytophotometry. All classical osteosarcomas regardless of histologic type (osteo-, chondro-, fibroblastic) or grade were found to be hyperploid (abnormally increased DNA content) while both paraosteal osteosarcomas proved to be diploid (normal DNA content). Closer analysis of the DNA distribution curves showed that the majority of the classical osteosarcomas exhibited a triploid modal DNA value and more than 90% hyperploid cells. Cytochemical characterization of osteosarcomas may be of prognostic significance in reflecting the degree of malignancy. The results of the present study indicate that cytophotometric DNA analysis, as an adjunct to conventional histologic evaluation, offers an objective means of differentiating between classical and paraosteal osteosarcomas.

Adolescent↗
PubMed1984

Changing metastatic patterns of osteosarcoma.

The clinical courses of 111 patients with osteosarcoma treated at UCLA between 1971 and 1982 were reviewed to ascertain the evolution of the natural history of this disease. Only patients with classic high-grade intraosseous osteosarcoma of the extremity, scapula, or pelvis were considered. Patients with low-grade parosteal osteosarcomas; primary osteosarcomas of the face, skull, vertebra, or ribs; and osteosarcomas arising in Paget's disease or previously irradiated bones were not included. Fifty-nine patients developed clinically evident distant metastases. Of these, 36 developed pulmonary metastases alone as the initial site of recurrence. Eighteen of 19 (94.7%) patients treated between 1971 and 1974 by amputation alone developed pulmonary relapse as the initial site of recurrence, whereas only 18 of 40 patients (45%) treated after 1974 with surgery and adjuvant chemotherapy developed pulmonary metastases alone as the initial site of recurrence. Although no patients in the early group developed an extrapulmonary metastasis as the initial site of recurrence, 11 of 40 patients (27.5%) treated with adjuvant chemotherapy developed an extrapulmonary metastasis as the initial site of recurrent disease, and 11 patients developed simultaneous pulmonary and extrapulmonary metastases. Although it is impossible to attribute this alteration in metastatic pattern to adjuvant chemotherapy alone, it is apparent that nonpulmonary metastases are becoming more common among patients currently treated for osteosarcoma.

Adolescent↗
PubMed1988

Prognostic significance of bone morphogenetic activity in osteosarcoma tissue.

The bone morphogenetic activities of the primary tumors of 30 patients with osteosarcoma were assayed. This activity was demonstrated as ectopic new bone formation on implantation of freeze-dried fractions of 12 of 30 tumors into athymic nude mice. Pulmonary metastases developed in ten (83%) of the 12 patients with osteosarcomas that produced bone morphogenetic protein (BMP), and bone metastases developed in six (50%) of the patients. The mean period from diagnosis to metastasis was 4.2 months in these patients. In contrast, pulmonary metastases developed in only eight (44%) of the patients with osteosarcomas that did not produce BMP, and bone metastases developed in only two (11%) of these patients. The mean period to metastasis was 12.3 months in these patients. The incidence of metastases in the patients with osteosarcomas producing BMP was significantly higher, and the mean period to metastasis was also significantly shorter than in the other group. The five year survival rates of patients with osteosarcomas that did and did not produce BMP were 33.3% and 54.6%, respectively (P = 0.015, log-rank test). Thus the bone morphogenetic activity of primary osteosarcoma tissue seems to be closely correlated with the prognosis of the patients.

Adolescent↗
PubMed1994

Expression of bone morphogenetic proteins in human osteosarcoma. Immunohistochemical detection with monoclonal antibody.

BACKGROUND: Bone morphogenetic proteins (BMP) induce ectopic bone formation in vivo and may play a role in normal bone development. In addition, bone morphogenetic activity, as measured in a bone-forming assay in immunodeficient, athymic nu/nu mice, is present in a proportion of osteosarcomas; this activity, which may be mediated by BMP, is correlated with a poor prognosis. METHODS: The development of a monoclonal antibody against recombinant human BMP-2, AbH3b2/17, has allowed immunohistochemical localization of BMP in tumor tissues. Cryostat sections of osteosarcomas (21 tumor samples), chondrosarcomas (5 samples), and Ewing's sarcomas of bone (5 samples) were examined with AbH3b2/17 using the avidin-biotin-immunoperoxidase method. RESULTS: The authors found AbH3b2/17 immunoreactivity in 12 of the 21 osteosarcoma samples (57% sensitivity) obtained from 20 patients. For one patient, samples of the primary lesion and a subsequent metastasis were tested, and only the latter showed AbH3b2/17 immunoreactivity. The chondrosarcomas and Ewing's sarcomas examined showed no immunoreactivity. In antigen-positive osteosarcomas, AbH3b2/17 immunostaining was localized predominantly in the cytoplasm of tumor cells. Moreover, the proportion of AbH3b2/17-reactive cells varied among osteosarcomas with disparate histologic features. CONCLUSIONS: The authors identified a rapid and widely applicable method for detecting BMP expression in intact tissues, which may complement and enhance the bone-forming assay in nu/nu mice as a prognostic procedure in osteosarcomas.

Adolescent↗
PubMed2002

ErbB2 expression is correlated with increased survival of patients with osteosarcoma.

BACKGROUND: Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma. METHODS: ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival. RESULTS: Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions.

Adolescent↗