Prognostic Markers in Chondrosarcoma: Evaluation of Cell Proliferation and of Regulators of the Cell Cycle

Scully, Sean P.; Layfield, Lester J.; Harrelson, John M.

doi:10.1080/13577149778344

Cited by 19 publications

(18 citation statements)

References 40 publications

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“…In accordance with previous studies, we observed a significant positive correlation between histologic tumor grade and proliferative activity assessed by MIB-1 proliferation marker expression in human chondrosarcomas [21,27,28]. Interestingly, we also found that MIB-1 proliferative index was significantly correlated with TGF-β1 and -β2 expression, while no correlation was evidenced for TGF-β3, suggesting that these factors could be important autocrine growth regulators in human chondrosarcomas.…”

Section: Discussionsupporting

confidence: 93%

Transforming growth factor-β isoform and receptor expression in chondrosarcoma of bone

et al. 2002

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It has been shown that transforming growth factor-beta (TGF-beta) has a potent stimulatory effect on the growth of chondrosarcoma cells in vitro. In order to examine the production of this family of growth factors and their receptors in vivo, we studied the expression of TGF-beta isoforms 1, 2, and 3 and of TGF-beta receptor types I and II (TGF-betaRI and TGF-betaRII) in a series of 24 chondrosarcomas of bone using immunohistochemistry and reverse-transcription polymerase chain reaction analysis. For comparison, five enchondromas and five osteochondromas were also analyzed. TGF-beta1 was expressed in 3 benign lesions (30%) and 18 chondrosarcomas (75%), with a significantly higher expression in grade-2 and -3 tumors than in grade-1 tumors ( P=0.002). TGF-beta2 was identified in 8 benign lesions (89%) and 21 chondrosarcomas (87.5%), with increased expression in grade-2 and -3 chondrosarcomas in comparison with grade-1 tumors ( P=0.05). TGF-beta3 was detected in 6 benign lesions (60%) and 17 chondrosarcomas (70.8%), with no significant differences between chondrosarcomas of different histologic grade ( P=0.6). Twenty-three chondrosarcomas (95.8%) expressed both TGF-beta receptor types I and II. Reverse-transcription polymerase chain reaction analysis performed on ten chondrosarcomas confirmed the presence of low or absent levels of TGF-beta1 and -beta2 mRNA in grade-1 chondrosarcomas, while grade-2 chondrosarcomas presented high levels of transcript of both cytokines. High levels of TGF-betaRI and RII mRNA were also detected. Chondrosarcomas with TGF-beta1 and TGF-beta2 overexpression (>20% of tumor cells) had a significantly higher expression of the cell proliferation marker MIB-1 ( P=0.006 and P=0.0003, respectively), while no significant correlation was found between TGF-beta3 expression and proliferative activity ( P=0.5). When TGF-beta isoform and receptor expression were examined with respect to disease-free survival, TGF-beta1 overexpression was significantly associated with a shorter disease-free survival ( P=0.004, log-rank test). Our data indicate that TGF-beta isoforms are produced by neoplastic cells of chondrosarcomas and could have a potential role as autocrine growth stimulators in these neoplasms.

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Section: Discussionsupporting

confidence: 93%

Transforming growth factor-β isoform and receptor expression in chondrosarcoma of bone

et al. 2002

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“…Some have found a significant correlation between DNA content, cell proliferation, hyperploidy, and survivorship in chondrosarcoma [38, 39, 40, 41, 42]. The relative expression of matrix metalloproteinase-1 to its inhibitor has also been associated with disease outcome in chondrosarcoma patients [35].…”

Section: Discussionmentioning

confidence: 99%

The Clinical Significance of Tenascin-C Splice Variant Expression in Chondrosarcoma

Ghert¹,

Jung²,

Qi³

et al. 2001

Oncology

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Objectives: Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix that is prominently expressed in malignant tumors. The purpose of this study was: (1) to determine the in vitro TNC splicing pattern in cultured human chondrocytes and chondrosarcoma cells, (2) to determine the in vivo TNC splicing pattern in clinical chondrosarcoma specimens, and (3) to perform survival analysis based on the TNC splicing pattern of the tumor specimens. Methods: Human articular chondrocytes and chondrosarcoma cells (cell line JJ012) were grown in a three-dimensional alginate bead system and harvested at two time points. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the in vitro TNC splicing pattern for the two cell types. Clinical chondrosarcoma specimens were obtained intra-operatively and underwent RT-PCR to determine the in vivo TNC splicing pattern. Specific immunohistochemical staining for the large TNC splice variant was performed on the clinical specimens. Survival analysis was used to determine the association between the specific TNC splicing pattern and survival. Results: The in vitro mRNA expression pattern of TNC in normal human articular chondrocytes was characterized by a high ratio of the small to the large splice variant (TNC_small:TNC_large), whereas the in vitro mRNA expression pattern for cultured chondrosarcoma cells was characterized by a low TNC_small:TNC_large ratio. Clinical chondrosarcoma specimens with a lower TNC_small:TNC_large ratio showed a trend towards decreased survival. The TNC splicing pattern of these specimens was verified through specific immunohistochemical staining for the large TNC isoform. Conclusions: The specific TNC splicing pattern may have clinical significance in chondrosarcoma. TNC expression may therefore play a future role in objecitve tumor grading and novel therapeutic approaches to this malignancy.

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“…Of the patients treated 29 had archival paraffin-embedded specimens and adequate clinical history to enable the following study. Paraffin-embedded specimens were sectioned and ten 10-µm sections were processed for mRNA isolation using Dynabeads oligo(dT) 25 and reverse transcribed with an oligo(dT) 16 primer. PCR was performed by using primers corresponding to novel sequences specific for MMP-1, MMP-8, MMP-13, and TIMP-1.…”

Section: Methodsmentioning

confidence: 99%

Collagenase specificity in chondrosarcoma metastasis

Scully

Berend

et al. 1999

Braz J Med Biol Res

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The treatment of some mesenchymal malignancies has made significant gains over the past few decades with the development of effective systemic therapies. In contrast, the treatment of chondrosarcoma has been limited to surgical resection, with the most significant prognostic indicators being surgical margins and histologic grade. We have reported that MMP-1/TIMP-1 gene expression serves to prognosticate for tumor recurrence in this group of patients. This led to the hypothesis that collagenase activity facilitates cell egression from the cartilaginous matrix. In the current study we examine the specificity of collagenase gene expression in archival human chondrosarcoma samples using semi-quantitative PCR. Messenger RNA was affinity extracted and subject to reverse transcription. The subsequent cDNA was amplified using novel primers and quantitated by densitometry. Ratios of gene expression were constructed and compared to diseasefree survival. The data demonstrate that the significance of the MMP-1/TIMP-1 ratio as a predictor of recurrence is confirmed with a larger number of patients. Neutrophil collagenase or MMP-8 was observed in only 5 of 29 samples. Collagenase-3 or MMP-13 was observed in all samples but the level did not correlate with disease-free survival. Since the collagenases have similar activity for fibrillar collagens and cleave the peptide in the same location, post-transcriptional regulatory mechanisms may account for the observed specificity. The determination of the MMP-1/TIMP-1 gene expression ratio not only serves to identify those patients at risk for recurrence but may also serve as a novel therapeutic avenue as an adjunct to surgical resection. Correspondence

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Prognostic Markers in Chondrosarcoma: Evaluation of Cell Proliferation and of Regulators of the Cell Cycle

Cited by 19 publications

References 40 publications

Transforming growth factor-β isoform and receptor expression in chondrosarcoma of bone

Transforming growth factor-β isoform and receptor expression in chondrosarcoma of bone

The Clinical Significance of Tenascin-C Splice Variant Expression in Chondrosarcoma

Collagenase specificity in chondrosarcoma metastasis

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