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Near-haploidy and subsequent polyploidization characterize the progression of peripheral chondrosarcoma.

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cytometry to demonstrate that near-haploidy is relatively frequent in peripheral chondrosarcomas. We performed fluorescence in situ hybridization (FISH) to interphase nuclei using centromeric probes, a genome wide loss of heterozygosity (LOH) analysis, and comparative genomic hybridization on five peripheral chondrosarcomas. We demonstrated near-haploidy in two low-grade tumors with only one copy and LOH of most chromosomes. Few chromosomes are disomic, with retention of heterozygosity and overrepresentation at comparative genomic hybridization. One tumor contains both a near-haploid clone with chromosomes in monosomic and disomic state, and an exactly duplicated clone. Two high-grade tumors clearly demonstrate polyploidization because most chromosomes show LOH and two copies at FISH, whereas few chromosomes have four copies with retention of heterozygosity. Using DNA from a relative, we demonstrate that chromosome loss is random regardless of parental origin. Using FISH on paraffin slides, we exclude near-haploidy to result from meiosis-like division in binucleated cells, characteristic for chondrosarcoma. In conclusion, our results indicate that near-haploidy characterizes the progression from osteochondroma toward low-grade chondrosarcoma. Moreover, further progression toward high-grade chondrosarcoma is characterized by polyploidization.

Adult↗

A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, chordoma and chordoma periphericum.

The present study is based on electron microscopical examinations of 15 conventional chondrosarcomas, 1 clear cell chondrosarcoma, 3 mesenchymal chondrosarcomas, 2 so-called chordoid sarcomas (extraskeletal myxoid chondrosarcoma), 4 sacrococcygeal chordomas, 2 ecchordoses and 1 neoplasm of tibia with features of a true peripheral chordoma (parachordoma). The neoplastic cells from various types of chondrosarcoma shared a number of features with nonneoplastic chondrocytes as e.g. a well-developed rough endoplasmic reticulum and microvillous cytoplasmic processes. In clear-cell chondrosarcoma, glycogen accumulation in the tumour cells was a prominent feature. The cells of mesenchymal chondrosarcoma usually showed the characteristics of immature mesenchymal cells. In contrast, chordomas commonly contained physaliferous cells with two types of vacuoles in their cytoplasm. The first type can be most adequately characterized as intracytoplasmic pseudoinclusions of intercellular substance, whereas the other type, glycogen-containing, single membrane-bound vacuoles most probably correspond to autophagosomes (cytolysosomes). Only vacuoles of the first type were recorded in the so-called chordoid sarcoma. They were also seen in chondrosarcomas. In contrast, both types of vacuoles were identified in the above-mentioned tibial tumour which, in addition, showed even other cytological characteristics of chordoma. The findings presented here have demonstrated distinct structural relationships between chordoid sarcoma and chondrogenic tumours. On the other hand, our observation of the uncommon tibial neoplasm indicates the possibility that tumours identical with chordoma may occur at sites other than the axial skeleton.

Bone Neoplasms↗

Cysteine proteinases in chondrosarcomas.

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathepsin mRNAs by Northern hybridisation, and for immunohistochemical localisation of the proteins. Northern analysis demonstrated the highest levels of cathepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, while cathepsin K was predominantly localised in large multinucleated osteoclastic cells and in some hypertrophic chondrocytes. These results suggest that chondrosarcoma can be included in the growing list of tumours, where cathepsins may well be involved in tumour progression. The simultaneous upregulation of cathepsins B and L, together with matrix metalloproteinase-13, and the association of cathepsin K with negative prognostic parameters suggests that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolytic enzymes. If this turns out to be the case, cathepsin inhibitors could provide the much needed adjuvant therapy for chondrosarcomas.

Adult↗

Cutaneous metastases as initial manifestation of dedifferentiated chondrosarcoma of bone. An autopsy case with review of the literature.

Metastases of chondrosarcoma to the skin are uncommon. We report a case of dedifferentiated chondrosarcoma that manifested as cutaneous metastases and had an outcome of three weeks. A 69-year-old male presented with two cutaneous nodules, one in the chest and other in the inguinal area. The punch biopsy of the latter showed a poorly differentiated mesenchymal metastatic tumor. Shortly before death, an X-ray revealed a proximal epiphyseal lesion in the right humerus, radiographically interpreted as chondrosarcoma. The autopsy showed this lesion to be a dedifferentiated chondrosarcoma whose nonchondroid mesenchymal part was akin, histologically and immunohistochemically, to the cutaneous metastases. While ten previous reports of chondrosarcoma metastatic to the skin are known, we believe that this is the first case to report the cutaneous metastases of the dedifferentiated variety. Furthermore, skin metastasis preceding the diagnosis of chondrosarcoma has not been previously reported. The fact that one part of this kind of tumor can be highly undifferentiated or, else, differentiated along lines not usually reminiscent of bone tumors, can make the diagnosis of such cases extremely difficult. Most chondrosarcomas metastatic to the skin arise in bones of the extremities, including the hand. The most common type of tumor is conventional chondrosarcoma. These metastases can be either single or multiple with a slight predilection for the head and neck region. Most patients die in a mean time of 6 months after the appearance of cutaneous metastases.

Aged↗

Chondrosarcoma in the young. A clinicopathologic analysis of 79 patients younger than 21 years of age.

We have studied 79 patients with chondrosarcoma who were younger than 21 years of age; this number represents 16% of all patients with chondrosarcoma diagnosed and treated in this hospital during half a century. The appendicular skeleton (53%), the humerus (13%), and the femur (23%) were most frequently affected. The pelvic bones were also common locations (20%). Pain, the presence of a mass, and tenderness were the most common presenting complaints. Two-thirds of the sarcomas were central lesions; the rest were mostly of the peripheral type. In 22 patients (28%), the chondrosarcomas were secondary to pre-existing benign solitary or multiple cartilaginous lesions. Histologically, the chondrosarcomas were subdivided into conventional, myxoid, "mesenchymal," and spindle cell (dedifferentiated) variants. Microscopically, the chondrosarcomas were graded according to their increasing grade of malignancy (grade I: 24 patients; grade II: 23 patients; grade III: 32 patients). Detailed survival analysis was performed and survival comparisons were made between the various age groups, the time of treatment, the sex of the patients, various skeletal sites, and the histologic grade of malignancy of the chondrosarcoma. It appears that chondrosarcoma affecting younger individuals is, in general, a more ominous tumor as compared with adults; i.e., relatively more high-grade chondrosarcomas affect young people than adults. Another notable difference was the dissimilarity in the skeletal distribution pattern of the malignant cartilage lesions between adults and the young.

Adolescent↗

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↗

[Bone resorption and remodelling in chondrosarcomas of the limbs and pelvis. Diagnostic value in 84 cases].

Aside well known histological and cytological arguments of malignancy, we have analysed the tumoral growth and invasion in periphery for the skeletal chondrosarcoma diagnosis. This study involves 84 cases of chondrosarcoma of limbs, and pelvic limb selected from 176 cases of chondrosarcoma seen in the Cochin hospital. The following constatations were made: the tumor growth is fast in a chondrosarcoma and the lesions are continuous; in a same case, we can assist to tumoral invasion signs and bone reparation signs. In the reverse, this growth is slow in an enchondroma and the lesions are the more often stabilized by a mature peri-tumoral osteogenesis. The residual bone fragments into the tumor are constant in the chondrosarcoma and more rare in the enchondroma. The peri-tumoral osteogenesis, identical to enchondral bone formation, is the more often immature in chondrosarcoma and always mature in enchondroma. The active bone resorption as well as the actual bone remodelling, are more frequent in the chondrosarcoma borders than the enchondroma those. Lastly, the peri-tumoral fibrosis is the own of enchondroma; its existence in the chondrosarcoma is only the reflection of a residual enchondroma.

Adolescent↗

An Integrated Clinical Genomic and Transcriptomic Subgrouping of Central Chondrosarcoma.

Central conventional chondrosarcoma, a malignant cartilage-producing bone tumor, is the second most common bone sarcoma. Chondrosarcomas are histologically graded, which is so far the best predictor of survival. Early mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are frequent, leading to the production of the oncometabolite D-2-hydroxyglutarate, which affects DNA methylation, resulting in a preferred chondrogenic differentiation over osteogenic differentiation of mesenchymal stem cells, which are currently considered the precursor cells of chondrosarcoma. DNA methylation profiling has previously revealed distinct profiles between IDH-mutant and IDH-wild-type chondrosarcomas, but the presence of further DNA methylation subgroups indicates that classification based solely on IDH status is too simplistic. In this study, we aim to identify biological subgroups in a total of 116 chondrosarcomas by integrating clinical data, IDH mutation status, gene expression, and genome-wide loss of heterozygosity (LOH). Clinical associations were observed between several factors, including sex and histological grade, as well as tumor site and IDH mutation status. RNA sequencing and genome-wide LOH confirmed the distinction between IDH-wild-type and IDH-mutant chondrosarcomas, where the number of chromosome arms affected by LOH was significantly higher in IDH-wild-type tumors than in IDH-mutant tumors. However, no clear subgroups emerged within each IDH group. Further clustering on RNA expression of differentiation markers identified subgroups characterized by chondrogenic, osteogenic, resting chondrocyte, or dedifferentiated profiles. These different subgroups showed a specific clinical presentation and suggest different precursor cells. Instead of a simple dichotomy between IDH-mutant and IDH-wild-type, our integrated approach highlights interconnected clinical, genomic, and transcriptomic patterns that offer a more nuanced view of chondrosarcoma biology and might potentially guide treatment stratification.

Humans↗

Chondrosarcoma of the larynx: the role of radiotherapy revisited--a case report and review of the literature.

BACKGROUND: Experience in the treatment of laryngeal chondrosarcoma is based on about 250 cases reported to date. The standard therapy is conservative surgery. Radiotherapy has universally been regarded as ineffective in the treatment of this disease. METHODS: A patient with a laryngeal chondrosarcoma was observed for 11 years after radical radiotherapy. The literature on laryngeal chondrosarcoma was critically reviewed, with emphasis placed on radiotherapy. RESULTS: The review of the literature revealed that experience with radiotherapy of laryngeal chondrosarcoma has been lacking, with fewer than 10 cases with short follow-up documented up to now. Meanwhile, increasing evidence of the efficacy of radiotherapy in the treatment of skeletal chondrosarcoma has emerged. The authors report the first case of chondrosarcoma of the larynx in which radical radiotherapy resulted in a long term remission of more than 10 years. CONCLUSIONS: Radiotherapy should be considered when radical surgery is not feasible without severe mutilation. It should also be considered for the treatment of residual disease. Laryngectomy should be restricted to salvage treatment when radiotherapy fails. In this study, radiotherapy appeared to be an effective modality in the treatment of low grade laryngeal chondrosarcoma, and these results contrast with the current widespread disapproval of this treatment.

Aged↗

Chondrosarcoma is not characterized by detectable telomerase activity.

Reactivation of telomerase, an enzyme which elongates human telomeres, is associated with cell immortilization. In approximately 90% of malignant tumours telomerase activity can be demonstrated, whereas in benign tumours it is mostly absent. Chondrosarcomas are relatively rare malignant cartilaginous neoplasms. A small number of chondrosarcomas located centrally in bone arise secondarily to an enchondroma, while the majority of chondrosarcomas developing from the surface arise within the cartilage cap of an osteochondroma. The histological distinction between a benign lesion and low-grade chondrosarcoma is generally considered difficult. To investigate whether the progression towards chondrosarcoma is characterized by reactivation of telomerase activity, this study determined telomerase activity in ten enchondromas, five osteochondromas, and 37 chondrosarcomas using the TRAP assay. In all tumour samples except one, telomerase activity was absent. By adding tumour lysates to the positive control, an increasing inhibition of telomerase activity was found with an increasing chondroid matrix, suggesting that it may contain inhibitory factors. Inhibition due to endogenous RNAse or Taq-polymerase inhibitors was excluded. The lack of detectable telomerase activity in the high-grade component of a dedifferentiated chondrosarcoma without matrix favours the possibility that telomerase is truly absent. Either its true absence or inhibitory effects disabling telomerase detection exclude the telomerase TRAP assay as a diagnostic tool in the differential diagnosis of benign and low-grade malignant cartilaginous tumours.

Biomarkers, Tumor↗

Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study.

The light and electron microscopic features of a well-differentiated chondrosarcoma with dedifferentiated foci (CDF) are compared with those of a poorly differentiated chondrosarcoma with spindle cell elements. The differentiation of this lesion from mesenchymal chondrosarcoma and from primitive multipotential primary sarcoma of bone is discussed. Ultrastructurally, the cells of the cartilaginous region of the CDF resembled those of the poorly differentiated chondrosarcoma and of the cartilaginous zones of an extraskeletal mesenchymal chondrosarcoma reported by Fu and Kay, and were characterised by an abundance of dilated endoplasmic reticulum and a scalloped and microvillous cell membrane. The stroma was devoid of mature crossbanded collagen fibers. The dedifferentiated portion was composed of mesenchymal-type cells surrounded by a relatively sparse matrix containing scanty mature collagen fibers; these cells resembled those in the cellular regions of the two previously documented mesenchymal chondrosarcomas but differed from the cartilaginous type cells in the cellular regions of the poorly differentiated chondrosarcoma.

Adult↗

Prognostic factors and outcome of pelvic, sacral, and spinal chondrosarcomas: a center-based study of 69 cases.

BACKGROUND: The surgical treatment of chondrosarcoma of the pelvis, sacrum, and spine is complex and technically demanding. As such, adequate surgical margins have been difficult to achieve, resulting in poor local control and survival. The objective of this study was to assess the outcome of patients with chondrosarcomas in these sites who were treated at a tumor center by using modern, aggressive surgical techniques and to identify prognostic factors. METHODS: Sixty-nine consecutive patients with chondrosarcoma of the pelvis (46 cases), sacrum (11 cases), and mobile spine (12 cases) who were treated at Sahlgrenska University Hospital from 1967 to 1999 were included in this study. Demographic information and follow-up data were obtained and statistically analyzed. RESULTS: There were 53 men and 16 women with a mean age of 45 years and a mean tumor size of 12 cm. There were 61 conventional chondrosarcomas, Grades 1-3 (with 13 arising in a preexisting osteochondroma) and 8 Grade 4 chondrosarcomas (7 dedifferentiated and one mesenchymal). The overall local recurrence rate was 27%, and the estimated overall 5- and 10-year survival rates were 72% and 67%, respectively. In contrast, the observed local recurrence rate was 3% (1 patient) in 31 patients whose conventional chondrosarcomas were resected with adequate surgical margins; 90% of these patients survived and most of them (26 of 31 or 84%) were continuously disease free. Significant factors associated with a worse prognosis with respect to local control and/or survival were high histologic tumor grade, increasing patient age, primary surgery outside of a tumor center, incisional biopsy versus a noninvasive diagnostic procedure, and inadequate surgical margins. CONCLUSIONS: Center-based diagnosis and treatment using modern aggressive surgical techniques significantly improve the prognosis of patients with chondrosarcoma of the pelvis, sacrum, and spine.

Adolescent↗

Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival.

Chondrosarcoma is a difficult musculoskeletal tumor to treat. Surgical treatment leads to severe disability, with high rates of local recurrence and life threat. No adjuvant therapy is effective in differentiated chondrosarcomas. Bisphosphonates (BPs) are a class of molecules which is effective in malignant bone diseases. The aim of the present study was to determine the effects of zoledronic acid (ZOL) on chondrosarcoma tumor progression. ZOL was tested in vivo (s.c. 100 microg/kg, twice a week) in a rat chondrosarcoma model and in vitro (10(-7)-10(-4) M) on cells derived from this model. Two types of animal models were assessed, the first simulated development after intralesional curettage, the second nonoperative development of the tumor. Cell proliferation, caspase-1, -3 activities and cell cycle analysis were studied. The results revealed that ZOL slows down primary tumor development, tumor progression after intralesional curretage and increases overall survival. ZOL inhibits cell proliferation and increases cell death, with no significant variation of caspase-1 and -3 activities and cell cycle profiles. The present study demonstrates for the first time that in addition to surgery, the therapy of chondrosarcoma with BPs might be beneficial. Because of these first results, new therapeutic approaches of chondrosarcoma must be considered, mainly for low grade chondrosarcoma when disabling operation is planned and when only intralesional resection can be undertaken.

Animals↗

Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression.

Loss of heterozygosity (LOH) at chromosomal band 9p21 is one of the few consistent genetic aberrations found in conventional chondrosarcoma. This locus harbours two cell-cycle regulators, CDKN2A/p16/INK4A and INK4A-p14ARF, which are inactivated in various human malignancies. It was therefore hypothesized that this locus also plays a role in the development of chondrosarcoma and this locus was investigated at protein, genetic, and epigenetic levels. Loss of p16 protein expression was detected by immunohistochemistry in 12 of 73 central chondrosarcomas and it correlated with increasing histological grade (p = 0.001). Loss of p16 protein expression was not found in 51 enchondromas, which are presumed to be potential precursors of conventional central chondrosarcoma. LOH at 9p21 was found in 15 of 39 chondrosarcomas (38%) but it did not correlate with loss of p16 protein expression. SSCP analysis of p16 did not reveal any mutations in 47 cases. Also, p14 was not the target of LOH, since it gave no aberrant bands on SSCP. To investigate whether an epigenetic mechanism was operating, methylation-specific PCR was used to look at p16 promotor methylation, which was identified in 5 of 30 tumours. However, this did not correlate with protein expression, or with LOH at 9p21. Cytogenetic data were available in a subset of cases. All tumours that showed chromosome 9 alterations also showed LOH and loss of INK4A/p16 protein expression. It is concluded that although some alterations were found at the DNA level and at the promoter expression level, the lack of correlation between LOH, promotor methylation, and protein expression indicates that a locus other than CDKN2A/p16 must be the target of LOH at 9p21. The correlation between INK4A/p16 protein expression and tumour grade, and the retention of expression in enchondromas, indicates that loss of INK4A/p16 protein expression may be an important event during tumour progression from enchondroma to conventional central chondrosarcoma, and in the progression in grade after recurrence of chondrosarcoma.

Adolescent↗

Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas.

Enchondromas and conventional central chondrosarcomas are, respectively, benign and malignant hyaline cartilage-forming tumours that originate in the medulla of bone. In order to gain a better understanding of the molecular process underlying malignant transformation of enchondroma, and to investigate whether there is a biological difference between conventional central cartilaginous tumours and those of enchondromatosis or with phalangeal localization, a series of 64 enchondromas (phalanx, n = 21; enchondromatosis, n = 15) and 89 chondrosarcomas (phalanx, n = 17; enchondromatosis, n = 13) was collected. Indian Hedgehog (IHH)/parathyroid hormone related peptide (PTHrP) signalling, an important pathway in chondrocyte proliferation and differentiation within the normal growth plate, was studied by immunohistochemical analysis of the expression of PTHrP, PTHR1, Bcl-2, p21, cyclin D1, and cyclin E. Quantitative real-time PCR for IHH, PTCH, SMO, and GLI2 was performed on a subset of tumours. The data show that IHH signalling is absent in enchondromas and central chondrosarcomas, while PTHrP signalling is active. There was no difference in the expression of any of the molecules between 35 enchondromas and 26 grade I central chondrosarcomas, indicating that PTHrP signalling is not important in malignant transformation of enchondroma. Higher expression of PTHR1 and Bcl-2 was associated with increasing histological grade in chondrosarcoma, suggesting involvement in tumour progression. No difference was found between samples from enchondromatosis patients and solitary cases, suggesting no difference in PTHrP signalling. A small subset of phalangeal chondrosarcomas demonstrated down-regulation of PTHrP, which may be related to its more indolent clinical behaviour. Thus, in both enchondromas and central chondrosarcomas, PTHrP signalling is active and independent of IHH signalling, irrespective of the presence or absence of enchondromatosis.

Adolescent↗

Production of matrix metalloproteinases and a metalloproteinase inhibitor by swarm rat chondrosarcoma.

Chondrosarcoma was found to produce a heat-labile collagenase and a heat-stable collagenase inhibitor. Unlike its cartilage counterpart, the inhibitory activity in chondrosarcoma could only be detected after heat-treatment. Western blot analysis of chondrosarcoma-derived inhibitor showed that this inhibitor cross-reacted with a polyclonal antibody raised against purified cartilage-derived collagenase inhibitor (1) at a M.W. of about 33 kDa. In addition to the collagenase activity, which appears to be matrix metalloproteinase I (MMP-1), chondrosarcoma extracts were shown to contain four active gelatinase species which migrate at a molecular weight consistent with that reported for MMP-2 (72 kDa gelatinase, Type IV gelatinase) (2) and three active enzyme species which migrate at a molecular weight consistent with that reported for MMP-9 (92 kDa gelatinase, Type IV gelatinase) (3,4). In contrast, normal cartilage contained only two active and one latent form of MMP-2 in significantly lower amounts than in chondrosarcoma. In the case of MMP-9, the same three species were present in normal cartilage and in chondrosarcoma, but in lower amounts in the normal tissue. These results suggest that chondrosarcoma might develop in vivo because the inherent proteolytic balance between the protease(s) and its endogenous inhibitor(s) is shifted in favor of the enzyme.

Animals↗

[Clear cell chondrosarcoma of the larynx. A rare tumor in an uncommon location].

Clear cell chondrosarcoma is a rare bone tumor of low malignancy. It constitutes only 2% of all chondrosarcomas and shows a particular predilection for the epiphyses of long bones. So far, there have only been three cases of clear cell chondrosarcoma of the larynx published in the literature. We report the case of a 46 year old man who suffered from slowly worsening dyspnoea. Diagnostic evaluation revealed a directly subglottic stenosis of the larynx, narrowing the lumen to 1/3. When we tried to resect the stenosis via splitting the ring cartilage from outside, tumorous infiltration of the whole ring cartilage was found. Extended biopsies were taken and histology revealed a clear cell chondrosarcoma. The therapy of choice for this tumor is wide surgical resection. Additional radio- and/or chemotherapy are not recommended. Therefore, the patient underwent laryngectomy. Histologically, the clear cell chondrosarcoma can be easily confused with the highly malignant osteosarcoma or the conventional chondrosarcoma, both requiring more aggressive treatment. Thus, clear cell chondrosarcoma should be kept in mind and, when necessary, a reference histology by a bone tumor register should be requested.

Chondrosarcoma↗

Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells.

The histological grade of chondrosarcoma correlates well with their clinical behavior and with the patient's survival duration. We have previously demonstrated that p21 was expressed in the hypertrophic chondrocytes of the growth plate. To assess the relationship of p21 (waf1/cip1) to cell differentiation in chondrosarcoma, we examined the p21 expression in 14 cases of chondrosarcoma immunohistochemically and the induction of p21 by insulin-like growth factor-I (IGF-I) during cell differentiation in SW1353 chondrosarcoma cells. p21 immunoreactivity was seen in well-differentiated chondrosarcoma cells and was mutually exclusive with MIB1 reactivity in grade-1 chondrosarcoma. In vitro, the proteoglycan synthesis of SW1353 cells was increased by IGF-I in a dose-dependent manner. However, cell proliferation was not markedly stimulated. Overexpressions of p21 mRNA and p21 protein in SW1353 cells were induced by IGF-I 100 ng/ml. Our results suggested that the p21 expression was directly related to tumor differentiation and that the p21 expression was an important mediator for IGF-I in chondrosarcoma cells.

Antigens, Nuclear↗