Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma

Correlation with overall survival in 105 patients

Paul M. Armistead, Jason Salganick, Jae S. Roh, Dejka M. Steinert, Shreyaskumar Patel, Mark Munsell, Adel K. El-Naggar, Robert S. Benjamin, Wei Zhang, Jonathan Trent

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

BACKGROUND. Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first-line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies. METHODS. Paraffin-embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS). RESULTS. Of the 105 patients, 44 (42%) were female and 89 (85%) were older than 10 years of age. The 5-year OS for this cohort was 24.7%, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c-erb-b2 to be present on <10% of tumors but EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax were present in >40% of tumors. Patients whose tumors expressed PDGFR-α were found to have a shorter median OS by multivariate analysis (26 vs 266 months, P = .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months, P = .047). CONCLUSIONS. EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR-α and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy.

Original languageEnglish
Pages (from-to)2293-2303
Number of pages11
JournalCancer
Volume110
Issue number10
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Rhabdomyosarcoma
Receptor Protein-Tyrosine Kinases
Survival
Neoplasms
Phosphotransferases
Therapeutics
Survival Analysis
Paraffin
Multivariate Analysis
Immunohistochemistry
Drug Therapy

Keywords

  • Bax
  • Bcl-2
  • EGFR
  • PDGFR-α
  • PDGFR-β
  • Rhabdomyosarcoma
  • RMS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Armistead, P. M., Salganick, J., Roh, J. S., Steinert, D. M., Patel, S., Munsell, M., ... Trent, J. (2007). Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma: Correlation with overall survival in 105 patients. Cancer, 110(10), 2293-2303. https://doi.org/10.1002/cncr.23038

Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma : Correlation with overall survival in 105 patients. / Armistead, Paul M.; Salganick, Jason; Roh, Jae S.; Steinert, Dejka M.; Patel, Shreyaskumar; Munsell, Mark; El-Naggar, Adel K.; Benjamin, Robert S.; Zhang, Wei; Trent, Jonathan.

In: Cancer, Vol. 110, No. 10, 15.11.2007, p. 2293-2303.

Research output: Contribution to journalArticle

Armistead, PM, Salganick, J, Roh, JS, Steinert, DM, Patel, S, Munsell, M, El-Naggar, AK, Benjamin, RS, Zhang, W & Trent, J 2007, 'Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma: Correlation with overall survival in 105 patients', Cancer, vol. 110, no. 10, pp. 2293-2303. https://doi.org/10.1002/cncr.23038
Armistead, Paul M. ; Salganick, Jason ; Roh, Jae S. ; Steinert, Dejka M. ; Patel, Shreyaskumar ; Munsell, Mark ; El-Naggar, Adel K. ; Benjamin, Robert S. ; Zhang, Wei ; Trent, Jonathan. / Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma : Correlation with overall survival in 105 patients. In: Cancer. 2007 ; Vol. 110, No. 10. pp. 2293-2303.
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abstract = "BACKGROUND. Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first-line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies. METHODS. Paraffin-embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS). RESULTS. Of the 105 patients, 44 (42{\%}) were female and 89 (85{\%}) were older than 10 years of age. The 5-year OS for this cohort was 24.7{\%}, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c-erb-b2 to be present on <10{\%} of tumors but EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax were present in >40{\%} of tumors. Patients whose tumors expressed PDGFR-α were found to have a shorter median OS by multivariate analysis (26 vs 266 months, P = .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months, P = .047). CONCLUSIONS. EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR-α and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy.",
keywords = "Bax, Bcl-2, EGFR, PDGFR-α, PDGFR-β, Rhabdomyosarcoma, RMS",
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T2 - Correlation with overall survival in 105 patients

AU - Armistead, Paul M.

AU - Salganick, Jason

AU - Roh, Jae S.

AU - Steinert, Dejka M.

AU - Patel, Shreyaskumar

AU - Munsell, Mark

AU - El-Naggar, Adel K.

AU - Benjamin, Robert S.

AU - Zhang, Wei

AU - Trent, Jonathan

PY - 2007/11/15

Y1 - 2007/11/15

N2 - BACKGROUND. Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first-line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies. METHODS. Paraffin-embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS). RESULTS. Of the 105 patients, 44 (42%) were female and 89 (85%) were older than 10 years of age. The 5-year OS for this cohort was 24.7%, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c-erb-b2 to be present on <10% of tumors but EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax were present in >40% of tumors. Patients whose tumors expressed PDGFR-α were found to have a shorter median OS by multivariate analysis (26 vs 266 months, P = .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months, P = .047). CONCLUSIONS. EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR-α and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy.

AB - BACKGROUND. Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first-line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies. METHODS. Paraffin-embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS). RESULTS. Of the 105 patients, 44 (42%) were female and 89 (85%) were older than 10 years of age. The 5-year OS for this cohort was 24.7%, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c-erb-b2 to be present on <10% of tumors but EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax were present in >40% of tumors. Patients whose tumors expressed PDGFR-α were found to have a shorter median OS by multivariate analysis (26 vs 266 months, P = .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months, P = .047). CONCLUSIONS. EGFR, PDGFR-α, PDGFR-β, Bcl-2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR-α and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy.

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KW - Bcl-2

KW - EGFR

KW - PDGFR-α

KW - PDGFR-β

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DO - 10.1002/cncr.23038

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