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PubMed1990

Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases.

Canine extraskeletal osteosarcomas are extremely rare tumors. Over a period of 25 years at the Animal Medical Center, approximately 1,000 cases of skeletal osteosarcomas have been diagnosed. During the same period 11 cases of extraskeletal osteosarcomas and three extraskeletal chondrosarcomas were diagnosed. Tumors of the mammary gland were excluded. Extraskeletal osteosarcomas were found in the adrenal gland, eye, gastric ligament, ileum, kidney, liver, spleen, testicle, and vagina. The chondrosarcomas were found in the mitral valves, lungs, and omentum. The mean age of the dogs with extraskeletal osteosarcoma was 11 years, and the mean age of the dogs with extraskeletal chondrosarcoma was 14 years. The The sizes of the tumors ranged from 3 cubic centimeters to 8,315 cubic centimeters. Osteoblastic osteosarcomas were the most common histologic type (7/11, 63.6%); there was a single case of each of the following: fibroblastic, fibrous histiocytic, chondroblastic, and mixed osteo-chondroblastic osteosarcoma. Two of the dogs with chondrosarcomas had mesenchymal chondrosarcomas involving the lungs and omentum. The remaining dog had a regular chondrosarcoma involving the mitral valve. Distant metastases were present in seven of 11 dogs with extraskeletal osteosarcoma and in none of the dogs with chondrosarcoma. In contrast to human beings, in which most extraskeletal osteosarcomas occur in the soft tissues and the extremities, most canine extraskeletal osteosarcomas develop in the visceral organs.

Animals↗
PubMed2004

p21WAF1/CIP1 gene DNA sequencing and its expression in human osteosarcoma.

BACKGROUND: Mutation and expression change of p21WAF1/CIP1 may play a role in the growth of osteosarcoma. This study was to investigate the expression of the p21WAF1/CIP1 gene in human osteosarcoma, p21WAF1/CIP1 gene DNA sequence change and their relationships with the phenotype and clinical prognosis. METHODS: p21WAF1/CIP1 gene in 10 normal people and the tumours of 45 osteosarcoma patients were examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with silver staining. The PCR product with an abnormal strand was sequenced directly. The p21WAF1/CIP1 gene mRNA and P21 protein of 45 cases of osteosarcoma were investigated by using in situ hybridization and immunohistochemistry, respectively. RESULTS: The occurrence of P21 protein in osteosarcoma was 17.78% (8/45), and p21WAF1/CIP1 mRNA expression in osteosarcoma was 42.22% (19/45). The p21WAF1/CIP1 gene DNA sequencing of amplified production showed that in p21WAF1/CIP1 gene exon 3 of 36 cases of human osteosarcoma, there were 17 cases (47.22%) with C-->T at position 609; 10 normal blood samples' DNA sequence analysis yielded 8 cases (80.00%) with C-->T at the same position. CONCLUSIONS: Along with the increase of malignancy, the expression of p21WAF1/CIP1mRNA and P21 protein in osteosarcoma tends to decrease. It is uncommon for the p21WAF1/CIP1 gene mutation to occur in human osteosarcoma. As a result, the possible existence of tumour subtypes of p21WAF1/CIP1 gene mutation should be investigated. Our research leads to the location of p21WAF1/CIP1 gene polymorphism of Chinese osteosarcoma patients, which can provide a basis for further research.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1996

P53 gene abnormalities in osteosarcoma.

OBJECTIVE: The P53 tumor suppressor gene shows the most frequent genetic alteration in human tumors. Mutation, deletion and rearrangement of P53 gene have been found in several types of neoplasm including osteosarcoma. The present study is to clarify the status of abnormalities of this gene in osteosarcoma in China. MATERIALS AND METHODS: Forty-six osteosarcomas were collected from 32 male and 14 female patients aged 20.6 years on average. Eight patients had lung metastasis. Immunohistochemistry, Southern blot and contrast flow cytometry were used for the study. RESULTS: Twenty-seven of 46 (58.7%) osteosarcoma specimens showed strongly positive reaction to the MoAb BP53-12 staining (+2 - +3), which indicated overexpression of P53 protein in osteosarcoma. Contrast study with DNA flow cytometry made on osteosarcoma showed that most of the tumors with strongly positive P53 have higher DNA content than those of negative ones. Alterations of the restriction pattern of the P53 gene were detected in 4 of 20 osteosarcomas in the Hind III group and 3 of 24 in the Eco R I group. Three of them were part or whole deletion of the gene and five of them had extraband which indicated rearrangement of the gene. CONCLUSIONS: The results of this study showed that overexpression of P53 oncoprotein is one of the most frequent genetic changes in osteosarcoma and P53 oncoprotein expression analysis could be a prognostic parameter in osteosarcoma. P53 gene abnormalities play an important role in the development of transformation and proliferation of osteosarcoma cells.

Adult↗
PubMed1997

Second malignant neoplasms occuring in survivors of osteosarcoma.

BACKGROUND: Second malignant neoplasms have been noted infrequently in survivors of osteosarcoma treated before 1970. METHODS: For the above reason, the authors surveyed their patients to determine the actuarial incidence and relative risk of second malignancies among patients treated with adjuvant chemotherapy for osteosarcoma. RESULTS: Between March 1962 and March 1996, 334 patients received chemotherapy for newly diagnosed primary or metastatic osteosarcoma. Of these patients, 47 presented with metastases, 14 had multifocal osteosarcoma, and 273 had localized disease. Nine patients developed second malignant neoplasms 0.45-17.8 years (median, 6.3 years) after receiving definitive surgery and adjuvant chemotherapy for primary osteosarcoma; 2 of these patients had pulmonary metastasectomies before receiving adjuvant chemotherapy. The second neoplasms comprised two cases of malignant fibrous histiocytoma and one case each of melanoma, glioblastoma multiforme, chondrosarcoma, and carcinoma of the breast: stomach, colon, rectum. The overall 10-year cumulative incidence of second malignancies was 2% +/- 1%; by comparison, this rate was 2% +/- 1% for patients with localized osteosarcoma but was 8% +/- 5% (P = 0.15) for those who presented with metastatic disease. CONCLUSIONS: Since the advent of successful adjuvant chemotherapy, more patients are surviving primary osteosarcoma; therefore, the number of osteosarcoma patients who develop second malignancies can be expected to increase. Recognition of osteosarcoma patients who are members of families with Li-Fraumeni syndrome may lead to earlier intervention for these individuals.

Adolescent↗
PubMed1998

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma.

BACKGROUND: Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma. METHODS: Doxorubicin (adriamycin [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was assessed by ABA in 14 patients with primary osteosarcoma who were treated with preoperative chemotherapy containing ADM and 6 patients with relapsed osteosarcoma after intensive chemotherapy. Histologic responses to preoperative chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS: Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and demonstrated good histologic responses (>90% of %necrosis) to preoperative chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and demonstrated poor responses. Patients with recurrent osteosarcoma that was clinically evaluated to be resistant to previous chemotherapy also had low %AB (34.2+/-28.3%). CONCLUSIONS: Because the results of the current study revealed that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as well as chemotherapy without ADM for patients with osteosarcoma, and because ABA technically is simple and results can be assessed rapidly, the authors conclude that ABA is a clinically useful chemosensitivity test for patients with osteosarcoma.

Adolescent↗
PubMed1999

High grade surface osteosarcoma: a clinicopathologic study of 46 cases.

BACKGROUND: High grade surface osteosarcoma is a rare subtype of osteosarcoma arising on the surface of bone, accounting for only 8.9% of surface osteosarcomas at the study institution. METHODS: This study reviews 46 cases of high grade surface osteosarcoma, comprised of 13 cases from the Mayo Clinic files and 33 from the authors' files. Histologic features were reviewed in all cases, and radiographs were reviewed in 29 cases. RESULTS: There was a definite male predominance, and 70% of the patients were in the second and third decades of life. Forty-four of the 46 patients had lesions involving the long bones, the most common site being the midportion of the femur. Radiographically, the majority of lesions showed dense to moderate mineralization with a fluffy, immature appearance. Radiating spicules of bone perpendicular to the long axis of the bone, characteristic of periosteal osteosarcoma, were sparse. Histologic findings were identical to those of conventional osteosarcoma. Overall, survival at 5 years was 46.1%. Statistical analysis revealed that marginal excision was associated with an increased risk of local recurrence and that the patients with Broders Grade 3 tumors had a better prognosis than those with Grade 4 tumors. A good response to chemotherapy was associated with better clinical outcome. CONCLUSIONS: High grade surface osteosarcoma is a rare subtype of surface osteoscarcoma that has a prognosis similar to that of conventional osteosarcoma, in contrast to the more common type of osteosarcoma arising on the surface of bone. Wide excision and effective systemic chemotherapy are associated with better clinical results.

Adolescent↗
PubMed2006

Quantitative analysis of promoter hypermethylation in multiple genes in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common solid malignant diseases of childhood, occurring in approximately 6 children per million annually; however, to the authors' knowledge to date, the cause of osteosarcoma has remained mostly unknown. Genetic alterations of genes that are specific for osteosarcoma have not been identified. Genetic alternations in the status of DNA methylation, known as epigenetic alterations, are the most common molecular alterations in human neoplasia. Aberrant methylation in the promoter region of tumor-related genes is associated closely with epigenetically mediated gene silencing, which is a common feature in human tumors. METHODS: The authors analyzed CpG islands of 5 different gene loci for aberrant methylation profiles in 30 pairs of osteosarcoma and corresponding normal tissues by using the quantitative methylation-specific polymerase chain reaction method. The objectives of this study were to characterize the methylation changes in osteosarcoma more extensively and to identify epigenetic biomarkers that may be useful in the diagnosis and prevention of osteosarcoma. RESULTS: For the Ras effector homologue (RASSF1A), tissue inhibitor of metalloproteinase 3 (TIMP3), O-6-methylguanine DNA methyltransferase (MGMT), and death-associated protein kinase 1 (DAPK1) genes, significant differences were observed in the degree of hypermethylation between tumors and normal tissues (P < 0.01 and P < 0.001, respectively). Measurement of the cumulative multiple promoter hypermethylation revealed striking differences between tumor specimens and normal tissues (t = 7.31; P < .001). There also was a significant difference in the levels of DNA methylation between the metastatic and nonmetastatic high-grade osteosarcomas (t = 4.57; P < .01). In addition, the methylation levels were associated closely with gender (t = 6.44; P < .001). CONCLUSIONS: The results indicated that tumor tissues from patients with osteosarcoma had a significantly higher incidence of hypermethylation for several genes compared with corresponding normal tissues. The epigenetic changes observed in this study may have prognostic importance for patients with osteosarcoma.

Adolescent↗
PubMed1999

Common mechanisms of osteosarcoma and Paget's disease.

One of the most serious complications of Paget's disease is a significant increase in the incidence of osteosarcoma. Approximately 1% of Paget's patients develop osteosarcoma, an increase in risk that is several thousand-fold higher than the general population. This risk contributes significantly to the mortality and morbidity of Paget's disease patients. We examined several cases of pagetic and sporadic osteosarcoma for tumor-specific loss of constitutional heterozygosity (LoH) on chromosome 18q. Our analysis found that both pagetic and sporadic osteosarcoma tumors showed LoH for all or part of the distal portion of chromosome 18q. The pattern of LoH in both types of tumors identified a region between loci D18S60 and D18S42 that must contain the putative tumor suppressor locus. This region is tightly linked to familial Paget disease and familial expansile osteolysis (FEO). Our hypothesis is that the predisposition locus for Paget's disease and the tumor suppressor locus for osteosarcoma are either the same gene or that osteosarcoma in Paget's disease represents a deletion affecting two adjacent genes. In either model, localization of the osteosarcoma tumor suppressor gene would be of benefit in the eventual isolation of the predisposition locus for Paget's disease. We have begun to isolate and test candidate genes from within the region defined by both the familial Paget's disease families and the minimal region of LoH in osteosarcomas for evidence that one or more of them is responsible for predisposition to Paget's disease and/or osteosarcoma.

Bone Neoplasms↗
PubMed1996

SAS is amplified predominantly in surface osteosarcoma.

The development of several types of human tumors is related to amplification of genes that are involved in cell growth. The protein products of these genes give the cells a selective growth advantage. The q13-15 region of chromosome 12 is frequently altered in human sarcomas, and the SAS gene has been identified in an amplification unit mapping to this region. Gene amplification of SAS was analyzed to determine the frequency of genetic alteration of this gene in osteosarcoma. Using Southern blot analysis as well as quantitative polymerase chain reaction, SAS was found to be amplified in 10 (36%) of 28 osteosarcomas. Gene amplification was evaluated in subtypes of osteosarcoma. All seven surface osteosarcomas displayed amplified SAS. In contrast, SAS was amplified in only two (13%) of 15 intramedullary osteosarcomas. The finding that all surface osteosarcomas demonstrated SAS gene amplification suggests that this gene may play a role in the pathogenesis of osteosarcoma subtypes and that surface osteosarcoma may be genetically different from high-grade intramedullary osteosarcoma.

Blotting, Southern↗
PubMed2001

Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma.

Paget's disease of bone (PDB) is a common disorder characterized by focal areas of increased and disorganized osteoclastic bone resorption, leading to bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. Genetic factors play an important role in the pathogenesis of Paget's disease. In some families, the disease has been found to be linked to a susceptibility locus on chromosome 18q21-22, which also contains the gene responsible for familial expansile osteolysis (FEO)--a rare bone dysplasia with many similarities to Paget's disease. Insertion mutations of the TNFRSF11A gene encoding Receptor Activator of NF kappa B (RANK) have recently been found to be responsible for FEO and rare cases of early onset familial Paget's disease. Loss of heterozygosity (LOH) affecting the PDB/FEO critical region has also been described in osteosarcomas suggesting that TNFRSF11A might also be involved in the development of osteosarcoma. In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines. No specific abnormalities of the TNFRSF11A gene were identified in a Pagetic osteosarcoma, the osteosarcoma cell lines, DNA extracted from Pagetic bone lesions, or DNA extracted from peripheral blood in patients with familial or sporadic Paget's disease including several individuals with early onset Paget's disease. These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma.

Adult↗
PubMed1998

p53 gene mutations in osteosarcomas of low-grade malignancy.

Alterations in tumor suppressor gene p53, localized on chromosome 17p13, are considered to play a significant role in the initiation and, to some extent, even in the progression of various malignant tumors. In this respect, investigations on conventional highly malignant osteosarcomas have shown a mutation rate of approximately 20%. However, currently, data on the mutation rate in the group of variant histology osteosarcomas of low-grade malignancy do not exist. Therefore, we investigated a panel of low malignant entities (five low malignant intramedullary osteosarcomas grade 1; one intramedullary osteosarcoma grade 2; eight parosteal osteosarcomas, including one local recurrence grades 1 and 2, and five periosteal osteosarcomas grade 2) with polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis focusing on exons 4 to 8 of the p53 gene followed by direct sequencing. Point mutations were found in one low-grade osteoblastoma-like osteosarcoma and in two periosteal osteosarcomas grade 2 (one missense, one silent, and one nonsense mutation). This mutation rate of 15.7% (3 of 19) is comparable to that determined in highly malignant osteosarcomas. Moreover, the analysis of clinical data did not show any difference in the behavior of tumors with p53 mutations compared with those without. Therefore, we suggest that alterations in p53 gene are an early event in the tumorigenesis of malignant osteoblastic tumors without impact on progression of these tumors.

Adolescent↗
PubMed1985

Biological characterization of human bone tumors. V. Zonal characterization of osteosarcoma: topological biochemical analysis correlated with morphology.

Human osteosarcoma specimens were sliced in a cryomicrotome under strict morphological guidance. Serial sections of ten 10 micron slices each were collected in two groups according to morphologic criteria, one containing mostly undifferentiated tumor tissue, the other predominantly well-differentiated tumor tissue. The two series were analysed chemically for alkaline phosphatase (APase) acid phosphatase (acPase), beta-glucuronidase and proteolytic activities; protein, phosphorus, hydroxyproline, hexosamine, water and collagen contents were also determined. Four different types of osteosarcoma were studied: case 1 was a highly malignant osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma case 3 a well-differentiated osteosarcoma, and case 4 a highly malignant anaplastic osteosarcoma. The types of cases 1, 2 and 3 are known as osteoid-forming tumors. In their less well differentiated areas APase activity was about twice as high as in better differentiated osteosarcoma. In contrast, no APase was found in the wholly undifferentiated areas of case 4, while the enzyme showed a marked increase in the areas of incipient differentiation of this tumor. The matrix of tumors differs with regard to collagen and hexosamine contents, in accordance with the general state of differentiation. In general, increasing hexosamine contents together with decreasing hydroxyproline contents will reflect the anaplastic, dedifferentiated osteosarcoma. Calcification evident in the better differentiated areas of osteosarcoma is indicated by the phosphorus content, highest in case 2, with cases 3, 1, and 4 following in sequential order.

Acid Phosphatase↗
PubMed2000

[Multifocal osteosarcoma. A case report].

UNLABELLED: Multifocal osteosarcoma is an uncommon and aggressive presentation of osteosarcoma. CASE REPORT: We report a case of multifocal osteosarcoma in a 12-year-old boy who was admitted for a tumor of the skull, associated with pleural and pulmonary nodules. A computed tomography scan of the head showed a calcified lesion with intra- and extracranial extent. A biopsy of the skull tumor showed an osteoblastic osteosarcoma. Three weeks later, the patient developed two other tumors of the skull, a tumor of the left shoulder and a pelvic pain. Radiographic studies confirmed the presence of further lytic lesions at these sites. The patient was unresponsive to chemotherapy (high dose methotrexate and doxorubicin) and died nine months later. COMMENTS: Multifocal osteosarcoma, or osteosarcomatosis, is a highly aggressive form of osteosarcoma. The multiple lesions can all arise synchronously as primary tumors, or appear to be one dominant site with early and rapid appearance of secondary lesions. The incidence is reported to be between 1 and 10% of osteosarcoma. The histology shows an osteosarcoma of osteoblastic type in most cases. CONCLUSION: Despite intensive chemotherapy, the prognosis remains poor. The debate remains as to whether or not this clinical presentation represents true multifocality of the disease or a relatively unusual metastatic pattern of osteosarcoma.

Bone Neoplasms↗
PubMed2000

Antioxidants inhibit TNFalpha-induced motility and invasion of human osteosarcoma cells: possible involvement of NFkappaB activation.

Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.

Antioxidants↗
PubMed2000

Osteosarcoma of the pelvis--oncological results of 40 patients registered by The Netherlands Committee on Bone Tumours.

AIM AND METHODS: We reviewed the oncological outcome in 40 consecutive patients with an osteosarcoma of the pelvic region, registered in the files of the Netherlands Committee on Bone Tumours (NCBT) between 1978 and 1995. RESULTS: Six patients had distant metastases at initial presentation (Enneking stage IIIB), 33 patients had stage IIB osteosarcoma and one patient stage IB osteosarcoma. Patients with metastases were treated with chemotherapy (four) or palliative procedures (two). Patients with non-metastatic osteosarcoma were treated with surgical procedures with (14) or without (four) neoadjuvant chemotherapy, chemotherapy without surgical resection (nine), or palliative procedures (seven). The median survival of stage IIB and IIIB osteosarcoma was 14 months (2-175) and 7.5 months (2-16), respectively. Survival in patients with stage IIB osteosarcoma treated with curative procedures was significantly better (P<0.0006) compared with stage IIB patients treated with palliative intent. Two and 5-year survival for patients with curatively treated stage IIB osteosarcoma was 35% and 26%, respectively; distant metastases had developed in 65% of these patients. On univariate analysis, positive prognostic factors for patients with stage IIB osteosarcoma were complaints of 3 months or less before initial presentation, tumour size of 8 cm or less, osteoblastic subtype, surgical resection of the primary tumour and limb salvage procedures. CONCLUSION: In conclusion, the prognosis of pelvic osteosarcoma remained poor despite modern multimodality treatment regimens, including neoadjuvant chemotherapy.

Adolescent↗
PubMed2007

Primary osteosarcoma of the ovary: a case report and literature review.

Pure osteosarcomas, in which this tumor is not the mesenchymal component of a biphasic tumor, are only rarely encountered in the ovary. Herein, we report a case of a pure ovarian osteoarcoma and review all previously reported cases of ovarian involvement by osteosarcoma in the English literature. The latter includes (with the present case) 6 cases of pure osteosarcoma (Group A), 5 cases of osteosarcoma arising from a teratoma (Group B), and 2 cases of osteosarcomas of osseous origin (humerus and maxilla) metastatic to the ovary (Group C). The average ages of the Groups A, B, and C patients were 52.6, 52, and 37.5 years, respectively. The average tumor sizes in these groups were 13.46, 13.82, and 16 cm, respectively. There was no statististically significant difference between the Group A and B patients with respect to tumor size (P = 0.94) or age (P = 0.96) (t test). Eight of the 11 patients in groups A and B were FIGO stage 3 or 4 at presentation. Five (83%) of the 6 group A patients and 2 (40%) of the 5 group B patients died of their disease an average of 4.8 and 3.5 months after initial evaluations respectively. However, the 2 patients who presented with stage 1 disease (and with follow-up information) have shown no evidence of tumor recurrence at an average of 26 months' follow-up. It is concluded that ovarian osteosarcomas are rare malignancies that are frequently associated with teratomas but may be seen in pure form. Unlike osseous osteosarcoma whose peak age of incidence is in the second decade, ovarian osteosarcomas occur at an older age group. Most patients have advanced stage disease at presentation. Ovarian osteosarcomas have a high (>60%) case fatality rate; analysis of the reported cases suggests that the latter is attributable to the advanced stage at which most patients present, as there are no reported cases of patients with stage 1 disease whose diseases have recurred after surgical resection or who have died of their disease.

Aged↗
PubMed2006

Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5.

With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.

Adolescent↗
PubMed1984

Canine sinonasal skeletal neoplasms: chondrosarcomas and osteosarcomas.

We studied 34 chondrosarcomas and 17 osteosarcomas among 285 sinonasal neoplasms in the dog. Mesenchymal chondrosarcomas (24) were more common than ordinary chondrosarcomas. Ultrastructural studies done in one case confirmed mesenchymal chondrosarcoma. Of the osteosarcomas, fibroblastic osteosarcoma (7) was the most common. In contrast to non-sinonasal skeletal neoplasms which are composed mostly (80%) of osteosarcomas, chondrosarcomas (66%) and mesenchymal chondrosarcomas (47%) were predominant among the sinonasal skeletal neoplasms of this study. The average age (ten years) of the dogs with sinonasal osteosarcoma was higher than that of dogs with non-sinonasal skeletal osteosarcoma, and there was a distinct male predominance in the dogs with osteosarcoma and chondrosarcoma. Large breed dogs and boxers, frequently affected with skeletal neoplasms, were not affected commonly with sinonasal osteosarcoma. The frequency of metastasis in the dogs with chondrosarcoma and osteosarcoma was much lower than that seen in dogs with nonsinonasal skeletal neoplasms.

Age Factors↗