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At least 19 recordsLinked to original sources
PubMed2003

Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.

Adolescent↗
PubMed1993

Osteosarcoma. Low-grade intraosseous-type osteosarcoma, histologically resembling parosteal osteosarcoma, fibrous dysplasia, and desmoplastic fibroma.

BACKGROUND: Low-grade intraosseous osteosarcoma is a rare variety of osteosarcoma and it is difficult to recognize. METHODS: A series of 10 patients with low-grade intraosseous osteosarcoma is reported. These patients were identified from the Istituto Rizzoli files, which includes approximately 1000 cases of osteosarcoma. Clinical data and radiographic and histologic features were studied. RESULTS: The radiographic appearance confirmed malignancy in five patients and suggested it in two. A benign lesion was diagnosed in three patients. Three lesions resembled parosteal osteosarcoma, two appeared similar to fibrous dysplasia, and two had features of desmoplastic fibroma. A mixed histologic pattern was found in three other tumors. Recurrence after intralesional excision in all patients indicated the aggressive nature of this lesion. The development of metastases in two patients and progression in the grade of malignancy in one of these highlighted the malignant nature of the tumor. CONCLUSIONS: The correct diagnosis would permit adequate treatment with wide surgical margins.

Adolescent↗
PubMed2005

Primary hyperparathyroidism and osteosarcoma: examination of a large cohort identifies three cases of fibroblastic osteosarcoma.

UNLABELLED: To study a possible relationship between hyperparathyroidism and osteosarcoma, we reviewed 1234 osteosarcoma patients. In this cohort, only three patients had a diagnosis of both hyperparathyroidism and fibroblastic osteosarcoma. These results indicate that hyperparathyroidism is not more prevalent in patients with osteosarcoma than in the general population. However, the presence of hyperparathyroidism may modify the histologic and cytologic features of osteosarcoma. INTRODUCTION: The finding of osteosarcoma in rats receiving human PTH(1-34) raised the question of whether hyperparathyroidism might be a risk factor for development of osteosarcoma in humans. MATERIALS AND METHODS: To study a possible relationship between hyperparathyroidism and osteosarcoma, we reviewed the medical records of 1234 osteosarcoma patients seen at The M.D. Anderson Cancer Center since 1948. Our study focused on clinical, biochemical, radiologic, and histopathologic findings indicative of primary hyperparathyroidism and the features of osteosarcoma. RESULTS: Of the 1234 cases reviewed, 3 patients had a diagnosis of both primary hyperparathyroidism and osteosarcoma. In two cases, hyperparathyroidism preceded the osteosarcoma, and in one case, both conditions were diagnosed at the same time. In two cases with concomitant hyperparathyroidism and osteosarcoma, features of osteitis fibrocystica were identified. The third patient was treated for hyperparathyroidism 3 years before osteosarcoma was diagnosed. All three patients had histologic features of fibroblastic osteosarcoma, a type that accounts for no more than 20% of osteosarcomas. To assess whether the prevalence of hyperparathyroidism was greater than expected in the normal population, we compared the age- and sex-specific prevalence in our cohort to a population of healthy individuals in Tromso, Norway. This analysis showed no significant differences between the two populations, despite the fact that a higher prevalence of hyperparathyroidism (6.9% versus 1.6%) was noted in the 60- to 69-year-old female osteosarcoma age group. CONCLUSIONS: Our results indicate that hyperparathyroidism is not more prevalent in affected individuals with osteosarcoma than in the general population. The finding of fibroblastic osteosarcoma in all three patients raises the question of whether coexistent hyperparathyroidism may modify the cytologic and histologic features of the malignancy.

Adolescent↗
PubMed1998

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.

Bone Neoplasms↗
PubMed1995

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗
PubMed2006

Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma.

Ezrin is a cytoskeleton linker protein that is actively involved in the regulation of growth and metastatic capacity of cancer cells. Recently, it has been demonstrated that a significant correlation exists between high ezrin expression levels and the poor outcome of pediatric osteosarcoma patients. The expression of ezrin was compared in conventional high-grade and central low-grade osteosarcoma lesions to investigate the role of ezrin overexpression in the metastasis of osteosarcoma. We compared the expression levels of the ezrin protein in 32 cases of high-grade osteosarcomas and 21 cases of low-grade osteosarcomas using immunohistochemistry. Ezrin protein expression levels were examined in three different human osteosarcoma cell lines by Western blotting. In addition, the mRNA expression levels of ezrin in these osteosarcoma cell lines and control fibroblasts were evaluated by real-time quantitative PCR. Ezrin immunoreactivity was present in 43.7% of high-grade osteosarcoma specimens. All low-grade osteosarcomas were negative for ezrin. The expression of ezrin was detected by Western blotting in all three osteosarcoma cell lines. The tested osteosarcoma cell lines showed marked amplification of ezrin mRNA compared to control cells. Taken together, ezrin appears to play a role in the progression of tumors, such as the metastasis of osteosarcoma. However, further data are needed before ezrin can be considered in clinical decision-making about osteosarcoma patients.

Biomarkers, Tumor↗
PubMed1997

Comparison of primary osteosarcoma of flat bones with secondary osteosarcoma of any site.

BACKGROUND: The authors hypothesized that the outcomes for young patients who present with primary osteosarcoma of flat bones or secondary osteosarcoma after other primary malignancies are similar because the sites of these tumors rarely makes them amenable to complete surgical resection. METHODS: The authors reviewed their experience with 27 patients with primary osteosarcomas involving flat bones and 18 patients with secondary osteosarcomas of any site, evaluating treatment, metastatic patterns, and outcome. RESULTS: Eleven of the 27 primary osteosarcomas and 10 of the 18 secondary osteosarcomas were at least partially resectable at the time of initial diagnosis. At last follow-up, 10 of the 27 patients with primary flat bone osteosarcoma were alive, eight of whom were disease free. Three of 18 with the secondary osteosarcoma patients were alive, including one with locally recurrent disease after recent disease resections. Chemotherapy with single or combinations of agents rarely yielded responses for primary flat bone or secondary osteosarcomas. CONCLUSIONS: Outcome for both groups of patients was poor due to metastases and failure of local control. Sixteen of the 27 patients with primary osteosarcoma of flat bones died of their tumor; an additional patient died of doxorubicin-related cardiomyopathy and had microscopic disease in the primary site at autopsy. Thirteen of the 18 patients with secondary osteosarcoma died of their second metastatic cancer, 2 additional patients died of doxorubicin-related cardiomyopathy/coccidioidomycosis, and another of acute renal toxicity.

Adolescent↗
PubMed1995

Osteosarcoma of the trunk treated by multimodal therapy: experience of the Cooperative Osteosarcoma study group (COSS).

The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group (COSS) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis. They were compared to those of all patients with extremity osteosarcoma treated according to the same protocols. While tumors of the trunk comprised only 32 (4.8%) of 665 primary classical osteosarcomas, secondary osteosarcomas were much more likely to be located in bones of the axial skeleton (6 of 18, 33%). Patients with primary osteosarcoma of the axial skeleton were older (mean: 20.8 vs. 15.2 years, P < 0.01) and were more likely to present with metastases at diagnosis (34% vs 12%, P < 0.001) than those with primary extremity osteosarcoma. In contrast to extremity tumors, local surgical treatment failure was very common in osteosarcomas of the trunk. Complete tumor removal was achieved in less than half of all evaluable cases. The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors. In conclusion, while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy, successful treatment is often barred by primary metastatic disease and inability to control the local tumor site.

Adolescent↗
PubMed2005

Osteosarcoma of the hand and forearm: experience of the Cooperative Osteosarcoma Study Group.

BACKGROUND: Osteosarcoma is extremely rare in the hand and forearm. Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity. METHODS: Epidemiological, clinical, and histopathologic data were analyzed in 39 patients with osteosarcoma of the forearm or hand who were enrolled in studies of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group from 1977 to December 2000. In patients with high-grade osteosarcoma, the treatment entailed surgical resection in combination with chemotherapy, whereas patients with low-grade osteosarcoma underwent only surgery. RESULTS: The 5-year overall survival rate among the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2% +/- 6.4%. The 5-year event-free survival rate was 65.4% +/- 9.6%. Five of the eight patients with secondary metastases were in remission at the time of analysis. Four patients died of their disease, and two patients died of chemotherapy-related complications. The mean overall survival rate was 88.0% +/- 6.5% in patients treated by wide or radical tumor resection and was 75.0% +/- 21.7% in patients with nonwide margins of resection. Whether amputation or local resection was performed had no significant influence on the prognosis. All six patients whose osteosarcoma was not classified as high-grade central osteosarcoma were in remission at the time of analysis. CONCLUSIONS: The results demonstrate a remarkably high survival rate for patients with high-grade osteosarcoma of the hand and forearm and confirm that multiagent chemotherapy in combination with wide excision is a highly effective treatment for this malignant tumor.

Adolescent↗
PubMed2003

Osteosarcoma after allogeneic bone marrow transplantation. A report of four cases from the Cooperative Osteosarcoma Study Group (COSS).

Osteosarcoma, one of the most frequent secondary malignancies after the treatment of young patients with cancer, has only very rarely been observed in association with hematopoietic stem cell transplantation (HSCT). We report four patients who were identified by searching the database of the Cooperative Osteosarcoma Study Group (COSS) for patients whose osteosarcoma arose following HSCT. Transplant indications had been acute lymphoblastic leukemia (3). and sickle cell disease (1). and the stem cell source was bone marrow in all cases (three allogeneic, one syngeneic). All four had received chemotherapy with alkylators as part of their conditioning regimen and/or first line therapy. The conditioning regimen included total body irradiation in three patients. The osteosarcomas arose at the age (adolescence) and sites (around the knee) typical for the disease. All four patients received chemotherapy as part of multimodal osteosarcoma treatment, and all four are currently alive, three in continuous remission at 5 7/12, 2 11/12, and 0 6/12 years and one with relapsed osteosarcoma at 4 1/12 years. One of the osteosarcoma-free survivors suffered a third malignancy, myelodysplastic syndrome. Osteosarcoma should be included among the secondary malignancies that can arise following HSCT. Multi-modal therapy according to guidelines for de novo osteosarcoma can lead to long-term survival in selected patients.

Anemia, Sickle Cell↗
PubMed1999

Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group.

PURPOSE: The prognosis of osteosarcoma occurring as a second malignant disease (OS-SMD) is thought to be poor. We attempted to evaluate whether this holds true when OS-SMD is treated with combined modality therapy as developed for primary osteosarcoma and if factors that influence survival might be identified. PATIENTS AND METHODS: All patients with OS-SMD registered at the Cooperative German-Austrian-Swiss Osteosarcoma Study Group (COSS) study center between 1980 and June 1996 were evaluated for patient- and treatment-related factors, local and systemic outcome, and survival. Therapy was to be given according to contemporary COSS protocols for primary extremity osteosarcoma, including surgery and multiagent chemotherapy. RESULTS: Thirty patients with OS-SMD were registered (median latency period, 9 years 2 months). The first malignancies had been retinoblastoma (10 patients), sarcoma (10 patients), lymphoma (five patients), carcinoma (four patients), and medulloblastoma (one patient). Treatment for these malignancies had included radiotherapy in 24 patients, surgery in 20, and chemotherapy in 14. Twelve osteosarcomas were located axially and 18 were located in an extremity; 17 were radiation-related. Twenty-seven patients presented with localized disease; three presented with primary metastases (two skip, one lung). All 30 patients received chemotherapy, 29 with multiple drugs. Twenty-eight patients underwent operation. At 7 years, actuarial overall survival, survival free from osteosarcoma progression, and survival free from progression of any cancer were 50%, 34%, and 30%, respectively. In 24 patients with local tumor control, the corresponding values were 63%, 46%, and 38%. All seven local failures occurred in patients with axial osteosarcomas who did not undergo operation with wide surgical margins. CONCLUSION: Provided that local tumor control is achieved, OS-SMD treated with combined modality therapy may have a prognosis that approaches that of otherwise comparable primary osteosarcoma.

Adolescent↗
PubMed1992

A TP53 mutation detected in cells established from an osteosarcoma, but not in the retinoblastoma of a patient with bilateral retinoblastoma and multiple primary osteosarcomas.

A patient with bilateral retinoblastoma and subsequent multiple primary osteosarcomas has been described previously. Osteosarcoma cell lines established from this patient were shown to express a shortened RB1 mRNA transcript and no detectable normal Rb protein. We now show that the osteosarcoma cell lines have lost one TP53 allele and contain a mutation in exon 8 codon 286 [GAA to AAA (Glu to Lys)] in the remaining allele. Consequently, the osteosarcoma cell lines have no normal Rb protein and no normal p53 protein. Neither constitutional DNA nor DNA extracted from a retinoblastoma of the left eye of the patient contained the TP53 mutation, suggesting that the TP53 mutation in the osteosarcoma cells may represent a tumor-promoting mutation, which confers a selective growth advantage. If both RB1 and TP53 are involved in the initiation of osteosarcoma, the mechanisms for development of the retinoblastoma and osteosarcoma tumors are different.

Base Sequence↗
PubMed1997

Tissue matrix protein expression in human osteoblasts, osteosarcoma tumors, and osteosarcoma cell lines.

Treatment for osteosarcoma is problematic because there are no prognostic markers. Diagnosis is primarily limited to cytologic grading. Oncogenesis alters cell structure therefore osteoblast tissue matrix proteins (extracellular matrix, cytoskeletal, intermediate filament, and nuclear matrix proteins), components of the cell substructure, are candidates for osteosarcoma markers. Structural proteins of the extracellular matrix, e.g. the collagens, are useful for diagnosis but not for tumors that produce little osteoid. To identify principal cellular tissue matrix proteins that distinguish normal from transformed human osteoblasts, their expression in normal osteoblasts, two osteosarcoma cell lines, and three primary osteosarcoma tumors were compared. The tumors were graded as (i) intermediate, (ii) high, and (iii) high grade recurrent. The 1-D SDS/PAGE profiles of the major components of the nuclear matrix and intermediate filament fractions from normal osteoblasts did not vary with biopsy site, age, or sex of patients. These profiles included known cytoskeletal proteins and OB250, a approximately 250 kD protein(s) observed in the intermediate filament fraction. A loss of protein bands, including OB250, was observed in the osteosarcoma cell lines and tumors. The intermediate and high grade tumors exhibited nearly identical protein profiles including potential tumor-specific proteins and collagen, consistent with the presence of intracellular collagen fibers in osteosarcoma. A microsequence was obtained for OT25, a novel low molecular weight protein observed in osteosarcoma cell lines. Fibrinogen gamma-chain, a protein that mediates cell adhesion was recovered from the high grade recurrent tumor.

Adult↗
PubMed2004

Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition.

Osteosarcoma is the most common highly malignant bone tumor with primary appearance during the second and third decade of life. It is associated with a high risk of relapse, possibly resulting from a developed resistance to chemotherapy agents. As a means to overcome osteosarcoma tumor cell resistance and/or to sensitize tumor cells to currently used chemotherapeutic treatments, we examined the role of human apurinic endonuclease 1 (APE1) in osteosarcoma tumor cell resistance and prognosis. Sixty human samples of archived conventional (intramedullary) osteosarcoma were analyzed. APE1 protein was elevated in 72% of these tissues and among those with a known clinical outcome, there was a significant correlation between high APE1 expression levels and reduced survival times. The remaining 28% of samples showed low expression of APE1. Given that APE1 was overexpressed in osteosarcoma, we decreased APE1 levels using silencing RNA (siRNA) targeting technology in the osteosarcoma cell line, human osteogenic sarcoma (HOS), to enhance chemo- and radiation sensitivity. Using siRNA targeted technology of APE1, protein levels were reduced by more than 90% within 24 hours, remained low for 72 hours, and returned to normal levels at 96 hours. There was also a clear loss of APE1 endonuclease activity following APE1-siRNA treatment. A decrease in APE1 levels in siRNA-treated human osteogenic sarcoma cells led to enhanced cell sensitization to the DNA damaging agents: methyl methanesulfonate, H(2)O(2), ionizing radiation, and chemotherapeutic agents. The findings presented here have both prognostic and therapeutic implications for treating osteosarcoma. The APE1-siRNA results demonstrate the feasibility for the therapeutic modulation of APE1 using a variety of molecules and approaches.

Adult↗
PubMed2001

Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma.

BACKGROUND: In some malignancies, p53 mutations are associated with tumor progression. To address the role of p53 mutations in the development and progression of osteosarcoma, the authors analyzed specimens from 247 patients with primary localized osteosarcomas and 25 patients with osteosarcomas that were metastatic at the time of diagnosis. The group included 27 matched biopsy-resection specimens and 21 biopsy-metastasis paired specimens. METHODS: The authors examined the nature and location of p53 mutations (exons 4-10) by polymerase chain reaction-single-strand conformation polymorphism and confirmed mutations by direct DNA sequencing. RESULTS: The overall frequency of p53 mutations was 22% (60 of 272 specimens), with 13 of 60 mutations located in exons 4 or 10. A similar proportion of localized osteosarcomas had alterations of the p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96). Patients who had p53 missense mutations were older compared with patients who had nonsense alterations or a wild type gene (P = 0.01). Examination of paired biopsy-resection and biopsy-metastasis specimens revealed that the p53 status was concordant between the biopsy and later tumor specimens in all patients. CONCLUSIONS: The p53 mutation status did not differentiate between patients who presented with a localized osteosarcoma and those who presented with metastases at the time of diagnosis. The current data indicate that p53 mutations are not late events in osteosarcoma tumor progression, because they are evident before the development of metastases. The inclusion of exons 4 and 10 increased the sensitivity of the analysis.

Adolescent↗
PubMed1979

Transplantable osteosarcoma in mice. Structural characterization of a transplantable osteosarcoma obtained in an allogenic system.

Light microscopic, histochemical and ultrastructural studies of a transplantable mouse osteosarcoma were carried out. The osteosarcoma grew in CBA mice after injection of cultured cells derived from a Dunn osteosarcoma. The tumour differed from the original Dunn osteosarcoma with respect to metastatic potential and structural features. The transplantable tumour was an anaplastic, richly vascularized fibroblastic osteosarcoma with alkaline phosphatase activity and rather sparse osteoid formation, resulting in death of the animals within 6 to 8 weeks. Virus particles were found intracellularly, mainly localized to cisterns of rough endoplasmic reticulum, and extracellularly often close to plasma membranes and collagen fibres. Sign suggestive of formation of collagen fibres by tumour cells were observed. A possible viral influence upon the tumour was suggested also by its growth behaviour in vitro. The results indicate that this new transplantable tumour, obtained in an allogenic system, represents a clonal derivative of the original Dunn osteosarcoma.

Animals↗
PubMed2001

[A case with lung metastasis of osteosarcoma occurred 21 years after the operation of osteosarcoma on left tibia].

The patient was a 38-years-old woman. A chest X-ray film demonstrated the presence of an abnormal lesion. Her past history included osteosarcoma on the left tibia for which she received amputation of the left inferior limb at 17 years of age without any relapse thereafter. Considering that the patient might have lung metastasis of osteosarcoma on the basis of lung biopsy performed under CT guide, and then a tumor was removed under the thoracoscope. The tumor, 2.8 x 2.2 x 2.1 cm in size, was located right under the pleura at left S10 with its inside being filled up with fragile necrotic tissues. When compared pathohistologically with the primary lesion of osteosarcoma which had occurred 21 years before, the lung tumor was almost identical in terms of the tumor cell morphology but had a higher cell density without evidence of osteoid formation. The diagnosis of lung metastasis of osteosarcoma was established on the basis of the clinical course and the immunohistochemical staining. It is extremely rare case that osteosarcoma recurs in the form of lung metastasis 21 years after the operation of primary lesion. We report this case as a valuable one to identify the prognosis of osteosarcoma and the development mechanism of lung metastasis.

Adult↗
PubMed1989

[Cis-dichlorodiammineplatinum in osteosarcoma. Osteosarcoma Cooperative Study Group report].

Thirty-two patients with primary osteosarcoma and 18 patients with advanced osteosarcoma were treated by iv or ia infusion of cisplatinum at a dose of 100 mg/m2 every three weeks. The efficacy of the agent for primary osteosarcoma was mainly estimated by X-ray findings and histologic examination. One patient had a partial response, and 7 patients had a minor response. Pathologic evaluation of the extent of the primary tumor necrosis was performed on 27 resected specimens. Eight of 27 cases showed a good response (Ayala III A less than). One of 18 patients with advanced osteosarcoma had a partial response, and 2 a minor response. Nausea and vomiting (88%), liver dysfunction (42%), leukopenia (36%), nephrotoxicity (20%) and auditory disturbance (20%) were the main side effects in 50 patients. However, side effects of cisplatinum were generally reversible. The results suggest that cisplatinum is effective against osteosarcoma and may enhance the therapeutic results in osteosarcoma.

Adolescent↗