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PubMed2001

H-ras oncogene mutation in dedifferentiated chondrosarcoma: polymerase chain reaction-restriction fragment length polymorphism analysis.

Dedifferentiated chondrosarcomas, which are known for their poor prognosis, are characterized by conventional chondrosarcoma with high-grade anaplastic components. Activating mutations in ras genes are a common genetic abnormality in human malignancies. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 20 formalin-fixed paraffin-embedded chondrosarcomas, comprising 11 cases of conventional chondrosarcoma (six Grade 1 cases and five Grade 2 cases) and nine cases of dedifferentiated chondrosarcoma, using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. H-ras mutations were only seen in two out of the nine cases of dedifferentiated chondrosarcoma (2/9, 22%) and they were not seen in any of the cases of conventional chondrosarcoma (0/11, 0%). Dedifferentiated chondrosarcomas had a worse prognosis than conventional chondrosarcomas (P < .01); among the patients with dedifferentiated chondrosarcomas, those with H-ras mutation (n = 2) tended to have a worse prognosis than those without (n = 7), although the difference was not statistically significant (P = 0.068). Our results would seem to suggest that H-ras mutation may occur during the course of dedifferentiation and may also have some effect on malignant potential.

Adult↗

PubMed2000

Dedifferentiated clear cell chondrosarcoma.

Dedifferentiation, a change in the histologic character and clinical behavior of a tumor to a more immature and aggressive one, occurs in approximately 11% of all chondrosarcomas. The original lesion is usually a low-grade chondrosarcoma. Clear cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy with a preference for the ends of long bones. It is usually curable by resection. Recurrence commonly follows inadequate surgery, and metastases to lung, brain, and bones can develop. However, dedifferentiation has not yet been described in association with clear cell chondrosarcoma. Three patients are described who were initially diagnosed as having clear cell chondrosarcoma of the femur. Two were treated with en bloc resection for a clear cell chondrosarcoma. One of these had an undifferentiated sarcoma in a local recurrence after 6 years. In the second, metastasis of the clear cell chondrosarcoma developed 5(1/2) years after surgery; autopsy revealed undifferentiated sarcoma in the lung, heart, and lumbar spine. The third patient had dedifferentiated clear cell chondrosarcoma at the time of resection following the biopsy diagnosis of clear cell chondrosarcoma. All three died with metastatic disease. These three patients represent three different manifestations of dedifferentiation-at initial diagnosis, at recurrence, and at metastasis. To our knowledge, this is the first description of dedifferentiation occurring in clear cell chondrosarcoma.

Adenocarcinoma, Clear Cell↗

PubMed2006

Rb-loss is associated with high malignancy in chondrosarcoma.

Loss of function of the human retinoblastoma gene (Rb) is a frequent genetic abnormality in human malignancies and causes a disturbance in the cell cycle and loss of normal proliferation and differentiation. We studied the loss of heterozygosity (LOH) of the Rb gene in 31 formalin-fixed, paraffin-embedded cartilaginous tumors using polymerase chain reaction. The tumors were subdivided into 8 cases of dedifferentiated (DD) chondrosarcoma, 17 cases of conventional chondrosarcoma (nine grade 1, seven grade 2 and one grade 3), 4 enchondromas and 2 chondroblastomas. Both components of DD chondrosarcoma, the low-grade and anaplastic components, were separated by a microdissection approach. The genetic data were correlated with the expression of the Rb protein examined by Rb immunohistochemistry. We found Rb-LOH in one grade 3 chondrosarcoma, and in the anaplastic component in 7 of 8 cases of DD chondrosarcoma (89% of all high-grade chondrosarcomas). All tumors with Rb-LOH were immunohistochemically Rb-negative. The only case of DD chondrosarcoma negative for Rb-LOH in both components of the tumor also showed weak expression of the Rb protein in the anaplastic component. All benign cartilaginous tumors, low-grade chondrosarcomas and low-grade tumor components of DD chondrosarcomas were negative regarding Rb-LOH but positive in Rb immunohistostaining. We concluded that Rb-LOH predominantly occurs in high-grade chondrosarcomas. However, it is not a marker for identifying low-grade tumors with a tendency towards progression or local recurrence.

Adolescent↗

PubMed1999

Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma.

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of a hereditary or sporadic exostosis (peripheral chondrosarcoma). Loss of heterozygosity (LOH) was studied by microsatellite analysis at the loci harboring the EXT genes (implicated in hereditary multiple exostoses), the EXT-like genes, and at 9p21, 13q14, 17p13, and chromosome 10. Nineteen of 20 peripheral chondrosarcomas showed LOH at all loci tested, while only 3 of 12 central chondrosarcomas exhibited LOH, restricted to 9p21, 10, 13q14, and 17p13. LOH at 9p21 did not appear to involve the CDKN2A gene, as assessed by SSCP analysis. DNA flow cytometry demonstrated a wide variation in the ploidy status in peripheral chondrosarcomas (DNA indexes, 0.56-2.01), whereas central chondrosarcomas were predominantly peridiploid. Near-haploidy found in peripheral chondrosarcomas could explain part of the high LOH percentages. Ki-67 immunohistochemistry suggested a higher proliferation rate in peripheral chondrosarcomas. Our results indicate that peripheral chondrosarcomas, arising secondarily to an exostosis, may obtain genetic alterations during malignant transformation, with subsequent genetic instability as demonstrated by a high percentage of LOH and a wide variation in ploidy status. In contrast, peridiploidy and a low percentage of LOH in central tumors suggest that a different oncogenic molecular mechanism may be operative.

Adolescent↗

PubMed2002

Molecular profiling of human chondrosarcomas for matrix production and cancer markers.

Chondrosarcoma is the second most common malignant bone tumor, characterized by production of abundant extracellular matrix resembling hyaline cartilage. To better understand the molecular pathogenesis of chondrosarcoma, we analyzed 12 chondrosarcomas for their production of connective tissue components and SOX9, a key regulator of normal chondrocyte differentiation. Furthermore, 10 chondrosarcoma samples were screened for additional changes in gene expression using cDNA array analysis. In Northern analysis, several tumors were found to express type II collagen mRNA at levels comparable to fetal cartilage used as a control. Interestingly, the highest levels of type II collagen mRNA were seen in 2 of the 3 grade 3 chondrosarcomas, which also exhibited the highest mRNA levels of SOX9 and "prechondrogenic" pro alpha 1(IIA) collagen. Expression of SOX9 in human chondrosarcomas is novel and suggests that chondrosarcomas originate from a multipotent stem cell committed to differentiation along the chondrogenic pathway. Results of the cDNA array analyses emphasize the heterogeneous nature of chondrosarcoma as no single transcript was systematically up- or downregulated in all tumors analyzed. Among the interesting changes observed was upregulation of decorin mRNA in 7 of the 10 tumors analyzed. Further studies are needed to determine whether decorin plays a role in the pathogenesis of chondrosarcoma. The cDNA arrays also revealed discrepancies from Northern and RNase protection analyses in transcript levels of matrix components, emphasizing the need to validate cDNA array data with other techniques.

Adult↗

PubMed1993

Borderline chondrosarcoma of long and flat bones.

We reviewed histological and clinical findings of six cases of borderline chondrosarcoma and examined the expression of collagen types I, II, III, V, and VI by immunohistochemical analysis of these tumors. Borderline chondrosarcoma is defined as a cartilaginous tumor of bone resembling enchondroma on the basis of histomorphology. Clinically the tumor causes intermittent vague pain unrelated to physical activities. On radiographs borderline chondrosarcoma is characterized by evidence of endosteal erosion. We observed local recurrences in two cases treated by intralesional excision and marginal excision, and one of those cases died of inoperable local tumor recurrence. In our histological analysis based on tissue patterns, there were enchondromatous patterns in five cases, and chondrosarcomatous patterns in four cases. In the second recurrent tumor in one case, a chondrosarcomatous pattern was newly observed, and the recurrent tumor was found to be a low-grade chondrosarcoma cytologically in the other case. In the tumor matrix immunoreactivity for collagen types II and VI was predominant, with collagen types I, III, and V showing heterogeneous expression in some cases. In all cases rimming of tumor lobules with collagen types I and V was absent. Immunoreactivity for collagen type II in the cytoplasm of tumor cells was found in four cases and all three recurrent tumors. Borderline chondrosarcoma, as defined by histology, clinical symptoms and radiological appearance, shows a collagen distribution pattern similar to that of low-grade chondrosarcoma. These findings are in accordance with the clinical outcome of borderline chondrosarcoma which parallels that of low-grade chondrosarcoma. Thus borderline chondrosarcoma may be best treated by wide en-bloc excision rather than curettage.

Adult↗

PubMed1991

Histogenesis of clear cell chondrosarcoma. An immunohistochemical study with osteonectin, a non-collagenous structure protein.

The histogenesis of clear cell chondrosarcoma is still unclear: Apart from typical clear cell tumor areas, extensive production of woven bone formation suggests within the clear cell cartilagenous stroma is an intriguing phenomenon. Three cases of clear cell chondrosarcoma documented in the Bone Tumor Registry of Westphalia were examined for their patterns of osteonectin expression, and compared with other bone tumors of either osseous or cartilaginous origin, and with normal cartilage tissue. Found predominantly in osseous structures, the protein osteonectin takes part in the formation of new bone. The three clear cell chondrosarcomas showed a strong immunoexpression of osteonectin in clear cell, chondroid and in osseous tumor areas. Similarly, evidence of osteonectin was also found in osteoblastic and in chondroblastic osteosarcomas as well as in osteoblastomas. In contrast, osteonectin could not be demonstrated in the chondrosarcomas and mesenchymal chondrosarcomas from our registry that were analysed for comparison, and was found only minimally in the fibroblastic areas of dedifferentiated chondrosarcomas. The chondroblastic tumor components were always negative. There was no immunoexpression of osteonectin either in fetal or adult intervertebral disc tissue. The present immunohistochemical study of osteonectin has distinctly separated clear cell chondrosarcoma from the other variants of chondrosarcoma, and aptly verified the specificity of this entity. Moreover, the study would call for further histogenetic evaluation of clear cell chondrosarcoma, since the pattern of osteonectin expression in that tumor seems to indicate an osteogenic rather than a chondrogenic origin.

Adenocarcinoma↗

PubMed2004

Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula.

To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass ( p<0.0001), periosteal reaction ( p=0.008), cortical disruption in the juxta-articular fibula ( p=0.0133), cortical thickening ( p=0.032), and tumor size greater than 4 cm ( p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton.

Adolescent↗

PubMed2002

Intracranial extraskeletal myxoid chondrosarcoma: case report and review of the literature.

BACKGROUND: We describe a patient with an intracranial extra skeletal myxoid chondrosarcoma (EMC), an unusual neoplasm of the deep soft tissues of the extremities. Very rarely are they localised as an intracranial lesion, and we believe it is very important to accurately distinguish EMC from other intracranial tumours such as classical or "skeletal" chondrosarcomas, mesenchymal chondrosarcoma, enchondroma, and myxoid tumours (chordoma, and chondromyxoid fibroma) in order to determine their prognostic implications. Furthermore, this case presents with the second local recurrence, higher-grade cellular areas, such an event has never been reported in intracranial cases. METHOD: A 17 year-old female presented with tonic and clonic seizures, episodic left hemiplegia and intense right-sided headaches. Computed tomography and magnetic resonance of the skull showed a right fronto-parietal cortical lesion. Complete surgical excision of the lesion through a right parieto-temporal craniotomy was performed. The tumoral lesion recurred locally twice (16 and 19 months after the initial surgery respectively). FINDINGS: First and second surgical specimens where diagnosed as extra skeletal myxoid chondrosarcoma. Microscopically, the third specimen (second local recurrence) showed abrupt transition from areas of conventional myxoid chondrosarcoma to high-grade cellular areas with fusiform features. INTERPRETATION: Extra skeletal myxoid chondrosarcoma is very rarely described as an intracranial lesion. Reference on this topic is very confusing as there is no clear-cut distinction between skeletal chondrosarcomas with prominent myxoid matrix and extra skeletal myxoid chondrosarcoma which is a definite entity first defined by Enzinger and Shiraki in 1972 in deep soft tissues of the extremities. We review the cases reported in the literature with the diagnosis of myxoid chondrosarcoma either of extra skeletal origin or with skeletal attachment, and analyse their clinic and pathological features.

Adolescent↗

PubMed2005

Primary intradural myxoid chondrosarcoma: a case report and review in the literature.

OBJECTIVE AND IMPORTANCE: Chondrosarcomas are extremely rare cartilaginous tumours that typically usually are associated with bone. Therapeutic experience with primary spinal mesenchymal chondrosarcomas is also extremely limited. The exact origin of rare intradural spinal chondrosarcomas remains obscure. We report the first case in the literature of a primary intradural myxoid chondrosarcoma. CLINICAL PRESENTATION: This 40-year-old man experienced a 3 month history with back pain. The results of his neurological examination were normal. Magnetic resonance imaging (MRI)demonstrated at the T12 level intradural tumour. We could not identify this lesion as chondrosarcoma in preoperative period. INTERVENTION: At surgery, a mass found attached solely to pia mater, with a normal arachnoid and dura mater overlying was seen. The mass was excised completely and microscopic examination identified a myxomatous chondrosarcoma. The postoperative course was unremarkable. But a histological examination revealed primary myxoid chondrosarcoma. Experience with primary spinal mesenchymal chondrosarcomas is also extremely limited. We especially discussed to the histological examination. CONCLUSION: The differential diagnosis considered in the present case included meningioma, plasmacytoma, and non-neoplastic intradural spinal cord lesion. We emphasize the benefit of surgical resection without radiotherapy and/or chemotherapy. This case presents the first case in the literature of an primary spinal intradural myxoid chondrosarcoma.

Adult↗

PubMed2006

Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas.

Chordomas and chondrosarcomas are malignant tumors that are reported to have similar clinical presentations and radiological features but different behaviors and outcomes. The aim of this retrospective study was to determine whether specific radiological features of skull-base chordomas or chondrosarcomas are correlated with histopathology, and thus allow preoperative diagnosis. The study involved 32 classic chordomas, 6 chondroid chordomas and 4 chondrosarcomas (42 tumors total). For each case, tumor size and extent, the detailed anatomy involved, and magnetic resonance imaging and computed tomography findings were analyzed. Tumor extent was assessed using a novel method that assessed presence/absence in 18 defined skull-base zones. The chondrosarcomas presented significantly earlier in life than the chordomas (means, 20.5 years versus 36 years, respectively). At time of diagnosis, the median tumor volume was 23 cm(3) (range, 1.2-78.8 cm(3)) and the mean tumor extent was 6.7+/-2.9 zones. There were no differences between chordomas and chondrosarcomas, or between the two chordoma subgroups, with respect to lesion volume or extent. Comparison of other imaging findings revealed no features that were diagnostic for either chordoma or chondrosarcoma. The data support previous claims that chondrosarcomas present earlier in life than chordomas, but this finding is not diagnostic. There is wide variation in the extent of skull-base chordomas and chondrosarcomas, and in the specific anatomical structures these tumors involve. None of the MRI or CT features of these tumors appear to be useful for differentiating chordomas from chondrosarcomas preoperatively. For surgical planning, specific, area-oriented definition of tumor extent might provide more useful information than tumor-type classification schemes.

Adolescent↗

PubMed1995

Quantitative analysis of the plain radiographic appearance of central chondrosarcoma of bone.

RATIONALE AND OBJECTIVE: To quantitate radiographic features that distinguish the plain radiographic appearance of central chondrosarcoma from other solitary bone lesions. MATERIALS AND METHODS: Seven hundred nine cases of focal bone lesions, including 37 central chondrosarcomas, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of central chondrosarcoma in contrast with other lesions in the data base. RESULTS: The most specific appearance of long bone central chondrosarcomas was a lesion within the medullary cavity with geographic destruction, containing calcified matrix and a diameter greater than 5.9 cm, or arising within the proximal metaphysis or diaphysis. These features all are present in 9 (39%) of the 23 long bone central chondrosarcomas and in less than 1% of other lesions. In flat bone lesions, calcified matrix and either geographic bone destruction, medullary location, or enlargement of the host bone were 100% specific but of low sensitivity, identifying 7 (50%), 7 (50%), and 6 (41%) of the 14 flat bone chondrosarcomas, respectively. Inclusion of calcified matrix in the description is essential to make the criteria specific but excludes several of the most aggressive long bone chondrosarcomas. The vector analysis-generated differential diagnosis include osteosarcoma, fibrous dysplasia, unicameral bone cysts, aneurysmal bone cysts, malignant fibrous histiocytoma, and Ewing sarcoma. CONCLUSIONS: A relatively specific set of radiographic features can be defined to assist in plain film diagnosis of central chondrosarcoma, but there are many chondrosarcomas that fall outside these parameters. Thus, while not sufficiently sensitive to allow accurate plain film diagnosis in all cases, these criteria serve as an improved foundation for differential diagnosis.

Adolescent↗

PubMed2007

The effects of histone deacetylase inhibitors on the induction of differentiation in chondrosarcoma cells.

PURPOSE: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas. EXPERIMENTAL DESIGN: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines. We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo. RESULTS: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the alpha1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the alpha2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the alpha1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells. CONCLUSIONS: These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.

Apoptosis↗

PubMed2005

MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.

PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. MATERIALS AND METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.

Aneuploidy↗

PubMed1999

[Chondrosarcoma secondary to multiple cartilage diseases. Study of 29 clinical cases and review of the literature].

PURPOSE OF THE STUDY: Several studies have demonstrated better prognosis of chondrosarcomas arising in hereditary multiple exostosis or Ollier's disease. The aim of this study was to evaluate their clinical, radiological and histological features and compare their prognosis with other chondrosarcomas. MATERIAL AND METHODS: We reviewed twenty nine secondary chondrosarcomas among seventeen patients with osteochondroma (group A), and eight with Ollier's disease (group B). These tumors represented 12 p. 100 of all chondrosarcomas treated between 1950 and 1994 in Cochin Hospital. Two group B patients successively developed three multicentric chondrosarcomas. Twenty six resections (eight intra and eighteen extra-lesional), two disarticulations and one amputation were performed as primary treatment. The average follow-up of the study was 10.5 years. The results were evaluated by means of survival curves. The significance of the difference between the curves was determined by the log-rank test. RESULTS: The mean age of malignant change was 36 years old. The most frequent tumoral site was the innominate bone for group A and the femur for group B. In three cases, radiographs showed no malignant features. All chondrosarcomas were classified as grade 1 or 2. The ten-year survival rate was 82 p. 100 with no significant difference between the two groups. The survival rates were significantly different after carcinologic surgery (extra-lesional resection or amputation) and contaminated surgery (intralesional resection), with 5 and 88 p. 100 of local recurrences respectively. DISCUSSION AND CONCLUSION: These secondary chondrosarcomas represent about 10 p. 100 of all chondrosarcomas. They appear 15 years earlier. According to O'Neal and Ackerman classification, most of the tumors are well-differentiated (60 p. 100 grade I, 39 p. 100 grade II and 1 p. 100 grade III). Carcinologic surgery is generally curative. Ten-year survival rate is 94 p. 100. With equivalent grade and surgery, their prognosis is better as compared to primary chondrosarcomas.

Adult↗

PubMed1996

Prognostic significance of Ki67 (MIB1) proliferation index and p53 over-expression in chondrosarcomas.

To investigate the prognostic significance of the Ki67 (MIBI)-proliferation index and p53 over-expression in chondrosarcomas, we retrospectively analyzed a cohort of 29 patients with chondrosarcomas using immunohistochemical assays with MIBI and p53 monoclonal antibodies on formalin-fixed, paraffinembedded tissue samples with microwave preparation. We also assessed 19 patients with benign cartilaginous tumors as a control group. There was a significant positive correlation between MIBI index and tumor grade in chondrosarcomas, while there was no significant difference in the MIBI index between the grade-1 chondrosarcomas and the benign cartilaginous tumors. Patients categorized in the high-MIBI-index group had a significantly lower survival rate than those in the low-index group. Moreover, in analyzing the sub-set of the patients with grade-II chondrosarcomas, it was found that they could be prognostically sub-divided according to MIBI index. The p53 index also significantly correlated with patient survival, and there was significant correlation between the MIBI index and the p53 index. However, in multivariate analysis, only the MIBI index and tumor grade proved to be independent prognostic indicators of chondrosarcomas. These results demonstrate that the MIBI index can be a useful procedure for assessing tumor grade in chondrosarcomas, especially for determining the prognosis of patients with grade-II chondrosarcoma.

Adolescent↗

PubMed2003

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients.

PURPOSE: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas. PATIENTS AND METHODS: Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the "Gesellschaft für Schwerionenforschung" (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction. RESULTS: Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC degrees III have been observed. CONCLUSIONS: These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.

Adolescent↗

PubMed2006

Intrinsic radiation resistance in human chondrosarcoma cells.

Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16(ink4a), one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16(ink4a) contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16(ink4a) expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16(ink4a) expression on chondrosarcoma cell resistance to low-dose gamma-irradiation (1-5 Gy). p16(ink4a) expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16(ink4a) transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.

Acridine Orange↗