Prognostic significance of telomerase activity in soft tissue sarcomas.

Schneider-Stock, R.; Ryś, Janusz; Jaeger, Viola; Niezabitowski, A; Kruczak, Anna; Sokołowski, A.; Roessner, Albert

doi:10.3892/ijo.15.4.775

Cited by 10 publications

(15 citation statements)

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“…Two different markers, Hind III-digested lambda DNA (0.125-23.13 kb; New England Biolabs Inc., Beverly, MA) and 1 kb DNA ladder (0.25-10 kb; Life Technologies), were also loaded on the gel as length marker. The DNA was transferred by standard Southern Blotting and the blotting membranes were hybridized with a (TTAGGG) 4 probe labeled with Digoxigenin. Visualization of the signal was performed using a DIG luminescence detection kit (Roche, Mannheim, Germany).…”

Section: Telomere Length Measurementsmentioning

confidence: 99%

“…5 A rapid literature survey shows, however, that TA in STS may vary greatly, ranging from 17% 7 to 100% 9 of the cases examined. Some authors also found a positive correlation between TA and tumor aggressiveness in sarcomas 4 and, more specifically, in liposarcomas 5,6,9 whereas others did not. 3 Telomere length has rarely been examined in STS.…”

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confidence: 96%

“…Telomerase activity (TA) has been shown to be expressed in a majority of human carcinomas 1,2 but only few data exist regarding TA in sarcomas. [3][4][5][6][7][8][9] In a previous study, 3 we showed that TA is detectable in only about 50% of intermediate-/high-grade soft tissue sarcomas (STS) and undetectable in benign lesions and low-grade STS. These results are in keeping with those of Schneider Stock et al detecting TA in 38% (23/60) of their STS 4 and 69% of liposarcomas.…”

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confidence: 99%

“…[3][4][5][6][7][8][9] In a previous study, 3 we showed that TA is detectable in only about 50% of intermediate-/high-grade soft tissue sarcomas (STS) and undetectable in benign lesions and low-grade STS. These results are in keeping with those of Schneider Stock et al detecting TA in 38% (23/60) of their STS 4 and 69% of liposarcomas. 5 A rapid literature survey shows, however, that TA in STS may vary greatly, ranging from 17% 7 to 100% 9 of the cases examined.…”

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confidence: 99%

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Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Yan

Benhattar

Coindre

et al. 2002

Intl Journal of Cancer

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In a previous study, we showed that telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA expression were undetectable in benign mesenchymal lesions and low-grade soft tissue sarcomas (STSs), but detectable in about 50% of intermediate-/high-grade STSs. We wondered if this lack of TA or hTERT mRNA expression could be related to the tumor sample examined and if there was a relationship between the former 2 parameters and telomere length. Two separate tumor samples from 37 STSs were examined for telomerase activity, using the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA expression, using RT-PCR. Considerable attention has been drawn recently to the regulation of telomere length and telomerase activity in the process of cellular senescence and immortalization. 1,2 Human telomeres are specialized terminal chromosomal structures composed of TTAGGG repeats. Shortening of telomeres has been suggested to represent the mitotic clock of cell cycle; telomere shortening is observed in most dividing somatic cells, leading to cell senescence when reaching a critical level. 1,2 Telomerase, a ribonucleoprotein enzyme that is capable of synthesizing telomeric repeats, plays a pivotal role in the process of telomere length maintenance and cell immortalization. Telomerase activity (TA) has been shown to be expressed in a majority of human carcinomas 1,2 but only few data exist regarding TA in sarcomas. [3][4][5][6][7][8][9] In a previous study, 3 we showed that TA is detectable in only about 50% of intermediate-/high-grade soft tissue sarcomas (STS) and undetectable in benign lesions and low-grade STS. These results are in keeping with those of Schneider Stock et al. detecting TA in 38% (23/60) of their STS 4 and 69% of liposarcomas. 5 A rapid literature survey shows, however, that TA in STS may vary greatly, ranging from 17% 7 to 100% 9 of the cases examined. Some authors also found a positive correlation between TA and tumor aggressiveness in sarcomas 4 and, more specifically, in liposarcomas 5,6,9 whereas others did not. 3 Telomere length has rarely been examined in STS. 5,10 Examining a series of 30 sarcomas, Schneider-Stock et al. 10 showed that telomere TRF length was heterogeneous in this tumor category. Unfortunately, they didn't examine their tumors for TA and, thus, it was not known if telomere length correlated with TA or not. In a further study focusing on liposarcomas only, the same group found a positive correlation between the presence of TA, tumor aggressiveness, high tumor grade and high proliferative activity but not between TA and TRF length. This lack of correlation between TA and TRF length may have several causes including the activation of telomerase-independent mechanism(s) of telomere lengthening referred to as alternative lengthening of telomeres (ALT) 11-13 that seems to occur by means of telomeretelomere recombination. 13,14 In our first study on STS, we observed some degree of heterogeneity in TA expression when examining several, otherwise morphol...

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Section: Telomere Length Measurementsmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Yan

Benhattar

Coindre

et al. 2002

Intl Journal of Cancer

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“…In some mesenchymal tumors, for example, hTERT expression correlates with aggressive behavior. [23][24][25][26][27][28][29] Taken together, the above studies suggest that immunohistochemistry for hTERT could be used to predict aggressive behavior in giant-cell tumor of bone. Immunohistochemistry also allows direct visualization of the specific cell types with telomerase activity, a characteristic, which may be informative in heterogeneous tumors such as giantcell tumor.…”

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confidence: 84%

Distribution and prognostic significance of human telomerase reverse transcriptase (hTERT) expression in giant-cell tumor of bone

et al. 2008

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Giant-cell tumor of bone is considered a benign, locally aggressive and rarely metastasizing neoplasm of bone. Specific microscopic or radiographic findings that reliably predict behavior have remained elusive. However, recent evidence suggests that activity of the telomerase enzyme complex correlates with recurrence in giant-cell tumor, although the subset of cells with telomerase activity in these heterogeneous tumors has not been defined. In the present study, we investigated whether immunostaining for human telomerase reverse transcriptase, a component of the telomerase complex, correlates with outcome in giant-cell tumor and the distribution of telomerase reverse transcriptase staining in these tumors. We analyzed 58 cases of giant-cell tumor for the presence and pattern of telomerase reverse transcriptase immunostaining, presence of soft tissue involvement and the type of initial surgery, and correlated these findings with recurrence-free survival and metastasis-free survival. Specific staining with telomerase reverse transcriptase was present in 20 out of 58 tumors (35%) in the nuclei of mononuclear cells and, occasionally, osteoclast-like giant cells. Furthermore, positive telomerase reverse transcriptase immunohistochemistry correlated with recurrence-free survival (P ¼ 0.02), whereas the presence of soft tissue extension (P ¼ 0.3) and the type of initial surgery (P ¼ 0.2) did not. Only soft-tissue extension significantly correlated with metastasis-free survival (P ¼ 0.003). Therefore, telomerase reverse transcriptase expression may predict recurrence in giant-cell tumor insofar as positive immunostaining correlates with shorter recurrence-free survival and may be a useful prognostic marker to stratify patients to more aggressive treatment protocols.

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Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness

et al. 2001

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Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was observed and correlated with aggressiveness in different neoplasms such as breast, prostate, blood and brain cancers, among others. To investigate whether telomerase activity is an index of aggressiveness in bone and soft tissue lesions of the extremities, 66 biopsy samples from our tissue bank were studied. These samples included 43 high‐grade sarcomas, 9 aggressive benign tumors and 14 totally benign lesions. The samples were collected from patients homogeneously treated at the Rizzoli Orthopaedic Institute with a follow‐up ranging from 4 to 11 years (median, 7 years). A non‐radioactive polymerase chain reaction‐based enzyme‐linked immunosorbent assay was used for the study. All tumors investigated were positive for telomerase activity. Among benign lesions, only 2 aneurysmal bone cysts showed higher telomerase activity than the cut‐off point, whereas all the other benign lesions had lower activity. Our results indicate that high levels of telomerase activity in bone and soft tissue lesions correlate with more aggressive clinical behavior in patients treated with surgery alone. An interesting inverse correlation between telomerase activity and occurrence of pulmonary metastasis was detected in osteosarcoma patients treated with chemotherapy. A parallel increase of telomerase activity and malignancy was observed in the adipose and cartilagineous tissue lesions. Our data suggest that telomerase activity could be considered a marker of tumor aggressiveness for bone and soft tissue lesions. The results obtained in osteosarcoma samples suggest that low levels of telomerase activity may be predictive of the prognosis and should influence the therapeutic protocol. © 2001 Wiley‐Liss, Inc.

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Prognostic significance of telomerase activity in soft tissue sarcomas.

Cited by 10 publications

References 0 publications

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Distribution and prognostic significance of human telomerase reverse transcriptase (hTERT) expression in giant-cell tumor of bone

Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness

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