Telomere-maintenance mechanisms in soft-tissue malignant fibrous histiocytomas

Toshihiro Matsuo, Jerry W. Shay, Woodring E. Wright, Eiso Hiyama, Shoji Shimose, Tadahiko Kubo, Takashi Sugita, Yuji Yasunaga, Mitsuo Ochi

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21 Citations (Scopus)

Abstract

Background: Sarcomas are distinct from carcinomas in that a substantial portion of themuse the alternative lengthening of telomeres (ALT) mechanismto maintain their telomeres. The present study clarifies the prevalence of the ALT mechanism and examines the prognostic importance of telomere factors in soft-tissue malignant fibrous histiocytomas. Methods: We investigated a series of forty-three soft-tissue malignant fibrous histiocytoma samples from forty-three patients with regard to telomere length, telomerase activity, and human telomerase reverse transcriptase (hTERT) mRNA expression. Tumor samples were obtained from surgical specimens and were stored at -80°C until use. Univariate analysis of the tumor samples from patients for whom data were available on age, sex, histological grade, tumor size, surgical margin, recurrence, and telomere factors was performed with use of the log-rank test. Multivariate analysis with only significant variables was then performed. Results: Telomerase activity was detectable in 79.1% of the tumor samples, hTERT expression was demonstrated in 90.7% of the tumor samples, and evidence of engagement of the ALT mechanism of telomere length maintenance was observed in 32.6% of the tumor samples. Among the variables tested, ALT-positive status emerged as the only independent prognostic factor for death of the patient (hazard ratio, 0.275; 95% confidence interval, 0.104 to 0.724; p = 0.0089). There were no significant differences in survival rates between patients with ALT-positive, telomerase-positive tumors and those with ALT-positive, telomerase-negative tumors (p = 0.301) or between patients with ALT-positive tumors that showed above-average telomerase activity and those with ALT-positive tumors that showed below-average telomerase activity (p = 0.900). Therefore, telomerase activity does not affect the prognosis in patients with ALT-positive malignant fibrous histiocytoma. High telomerase expression is associated with a poor prognosis in patients with ALT-negative malignant fibrous histiocytoma (p = 0.0027). Conclusions: More detailed analysis will be needed to identify the most valuable prognostic factor in patients with malignant fibrous histiocytoma, and a more thorough understanding of telomere biology may give an indication of telomere-targeting therapy in the future. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Original languageEnglish (US)
Pages (from-to)928-937
Number of pages10
JournalJournal of Bone and Joint Surgery - Series A
Volume91
Issue number4
DOIs
StatePublished - Apr 1 2009

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Telomere Homeostasis
Malignant Fibrous Histiocytoma
Telomere
Telomerase
Maintenance
Neoplasms
Sarcoma

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

Telomere-maintenance mechanisms in soft-tissue malignant fibrous histiocytomas. / Matsuo, Toshihiro; Shay, Jerry W.; Wright, Woodring E.; Hiyama, Eiso; Shimose, Shoji; Kubo, Tadahiko; Sugita, Takashi; Yasunaga, Yuji; Ochi, Mitsuo.

In: Journal of Bone and Joint Surgery - Series A, Vol. 91, No. 4, 01.04.2009, p. 928-937.

Research output: Contribution to journalArticle

Matsuo, T, Shay, JW, Wright, WE, Hiyama, E, Shimose, S, Kubo, T, Sugita, T, Yasunaga, Y & Ochi, M 2009, 'Telomere-maintenance mechanisms in soft-tissue malignant fibrous histiocytomas', Journal of Bone and Joint Surgery - Series A, vol. 91, no. 4, pp. 928-937. https://doi.org/10.2106/JBJS.G.01390
Matsuo, Toshihiro ; Shay, Jerry W. ; Wright, Woodring E. ; Hiyama, Eiso ; Shimose, Shoji ; Kubo, Tadahiko ; Sugita, Takashi ; Yasunaga, Yuji ; Ochi, Mitsuo. / Telomere-maintenance mechanisms in soft-tissue malignant fibrous histiocytomas. In: Journal of Bone and Joint Surgery - Series A. 2009 ; Vol. 91, No. 4. pp. 928-937.
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abstract = "Background: Sarcomas are distinct from carcinomas in that a substantial portion of themuse the alternative lengthening of telomeres (ALT) mechanismto maintain their telomeres. The present study clarifies the prevalence of the ALT mechanism and examines the prognostic importance of telomere factors in soft-tissue malignant fibrous histiocytomas. Methods: We investigated a series of forty-three soft-tissue malignant fibrous histiocytoma samples from forty-three patients with regard to telomere length, telomerase activity, and human telomerase reverse transcriptase (hTERT) mRNA expression. Tumor samples were obtained from surgical specimens and were stored at -80°C until use. Univariate analysis of the tumor samples from patients for whom data were available on age, sex, histological grade, tumor size, surgical margin, recurrence, and telomere factors was performed with use of the log-rank test. Multivariate analysis with only significant variables was then performed. Results: Telomerase activity was detectable in 79.1{\%} of the tumor samples, hTERT expression was demonstrated in 90.7{\%} of the tumor samples, and evidence of engagement of the ALT mechanism of telomere length maintenance was observed in 32.6{\%} of the tumor samples. Among the variables tested, ALT-positive status emerged as the only independent prognostic factor for death of the patient (hazard ratio, 0.275; 95{\%} confidence interval, 0.104 to 0.724; p = 0.0089). There were no significant differences in survival rates between patients with ALT-positive, telomerase-positive tumors and those with ALT-positive, telomerase-negative tumors (p = 0.301) or between patients with ALT-positive tumors that showed above-average telomerase activity and those with ALT-positive tumors that showed below-average telomerase activity (p = 0.900). Therefore, telomerase activity does not affect the prognosis in patients with ALT-positive malignant fibrous histiocytoma. High telomerase expression is associated with a poor prognosis in patients with ALT-negative malignant fibrous histiocytoma (p = 0.0027). Conclusions: More detailed analysis will be needed to identify the most valuable prognostic factor in patients with malignant fibrous histiocytoma, and a more thorough understanding of telomere biology may give an indication of telomere-targeting therapy in the future. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.",
author = "Toshihiro Matsuo and Shay, {Jerry W.} and Wright, {Woodring E.} and Eiso Hiyama and Shoji Shimose and Tadahiko Kubo and Takashi Sugita and Yuji Yasunaga and Mitsuo Ochi",
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AU - Matsuo, Toshihiro

AU - Shay, Jerry W.

AU - Wright, Woodring E.

AU - Hiyama, Eiso

AU - Shimose, Shoji

AU - Kubo, Tadahiko

AU - Sugita, Takashi

AU - Yasunaga, Yuji

AU - Ochi, Mitsuo

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N2 - Background: Sarcomas are distinct from carcinomas in that a substantial portion of themuse the alternative lengthening of telomeres (ALT) mechanismto maintain their telomeres. The present study clarifies the prevalence of the ALT mechanism and examines the prognostic importance of telomere factors in soft-tissue malignant fibrous histiocytomas. Methods: We investigated a series of forty-three soft-tissue malignant fibrous histiocytoma samples from forty-three patients with regard to telomere length, telomerase activity, and human telomerase reverse transcriptase (hTERT) mRNA expression. Tumor samples were obtained from surgical specimens and were stored at -80°C until use. Univariate analysis of the tumor samples from patients for whom data were available on age, sex, histological grade, tumor size, surgical margin, recurrence, and telomere factors was performed with use of the log-rank test. Multivariate analysis with only significant variables was then performed. Results: Telomerase activity was detectable in 79.1% of the tumor samples, hTERT expression was demonstrated in 90.7% of the tumor samples, and evidence of engagement of the ALT mechanism of telomere length maintenance was observed in 32.6% of the tumor samples. Among the variables tested, ALT-positive status emerged as the only independent prognostic factor for death of the patient (hazard ratio, 0.275; 95% confidence interval, 0.104 to 0.724; p = 0.0089). There were no significant differences in survival rates between patients with ALT-positive, telomerase-positive tumors and those with ALT-positive, telomerase-negative tumors (p = 0.301) or between patients with ALT-positive tumors that showed above-average telomerase activity and those with ALT-positive tumors that showed below-average telomerase activity (p = 0.900). Therefore, telomerase activity does not affect the prognosis in patients with ALT-positive malignant fibrous histiocytoma. High telomerase expression is associated with a poor prognosis in patients with ALT-negative malignant fibrous histiocytoma (p = 0.0027). Conclusions: More detailed analysis will be needed to identify the most valuable prognostic factor in patients with malignant fibrous histiocytoma, and a more thorough understanding of telomere biology may give an indication of telomere-targeting therapy in the future. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

AB - Background: Sarcomas are distinct from carcinomas in that a substantial portion of themuse the alternative lengthening of telomeres (ALT) mechanismto maintain their telomeres. The present study clarifies the prevalence of the ALT mechanism and examines the prognostic importance of telomere factors in soft-tissue malignant fibrous histiocytomas. Methods: We investigated a series of forty-three soft-tissue malignant fibrous histiocytoma samples from forty-three patients with regard to telomere length, telomerase activity, and human telomerase reverse transcriptase (hTERT) mRNA expression. Tumor samples were obtained from surgical specimens and were stored at -80°C until use. Univariate analysis of the tumor samples from patients for whom data were available on age, sex, histological grade, tumor size, surgical margin, recurrence, and telomere factors was performed with use of the log-rank test. Multivariate analysis with only significant variables was then performed. Results: Telomerase activity was detectable in 79.1% of the tumor samples, hTERT expression was demonstrated in 90.7% of the tumor samples, and evidence of engagement of the ALT mechanism of telomere length maintenance was observed in 32.6% of the tumor samples. Among the variables tested, ALT-positive status emerged as the only independent prognostic factor for death of the patient (hazard ratio, 0.275; 95% confidence interval, 0.104 to 0.724; p = 0.0089). There were no significant differences in survival rates between patients with ALT-positive, telomerase-positive tumors and those with ALT-positive, telomerase-negative tumors (p = 0.301) or between patients with ALT-positive tumors that showed above-average telomerase activity and those with ALT-positive tumors that showed below-average telomerase activity (p = 0.900). Therefore, telomerase activity does not affect the prognosis in patients with ALT-positive malignant fibrous histiocytoma. High telomerase expression is associated with a poor prognosis in patients with ALT-negative malignant fibrous histiocytoma (p = 0.0027). Conclusions: More detailed analysis will be needed to identify the most valuable prognostic factor in patients with malignant fibrous histiocytoma, and a more thorough understanding of telomere biology may give an indication of telomere-targeting therapy in the future. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

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