PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme

Justin S. Smith, Issei Tachibana, Sandra M. Passe, Brenda K. Huntley, Thomas J. Borell, Nancy Iturria, Judith R. O'Fallon, Paul L. Schaefer, Bernd W. Scheithauer, C. David James, Jan Craig Buckner, Robert Brian Jenkins

Research output: Contribution to journalArticle

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Abstract

Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semi-quantitative polymerase chain reaction, and DNA sequenceing. All statistical test were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P<.001, respectively), and mutation of p53 was statisticaly significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma indentified PTEN (P = .002) and p53 (P = .012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performances score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of pro-longed survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

Original languageEnglish (US)
Pages (from-to)1246-1256
Number of pages11
JournalJournal of the National Cancer Institute
Volume93
Issue number16
StatePublished - Aug 15 2001

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Astrocytoma
Glioblastoma
Mutation
Chromosomes, Human, Pair 10
Survival
erbB-1 Genes
Neoplasms
Chromosomes, Human, Pair 7
p53 Genes
Survival Analysis
Fluorescence In Situ Hybridization
Glioma
Multivariate Analysis
Regression Analysis
Clinical Trials
Confidence Intervals
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Smith, J. S., Tachibana, I., Passe, S. M., Huntley, B. K., Borell, T. J., Iturria, N., ... Jenkins, R. B. (2001). PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. Journal of the National Cancer Institute, 93(16), 1246-1256.

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. / Smith, Justin S.; Tachibana, Issei; Passe, Sandra M.; Huntley, Brenda K.; Borell, Thomas J.; Iturria, Nancy; O'Fallon, Judith R.; Schaefer, Paul L.; Scheithauer, Bernd W.; James, C. David; Buckner, Jan Craig; Jenkins, Robert Brian.

In: Journal of the National Cancer Institute, Vol. 93, No. 16, 15.08.2001, p. 1246-1256.

Research output: Contribution to journalArticle

Smith, JS, Tachibana, I, Passe, SM, Huntley, BK, Borell, TJ, Iturria, N, O'Fallon, JR, Schaefer, PL, Scheithauer, BW, James, CD, Buckner, JC & Jenkins, RB 2001, 'PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme', Journal of the National Cancer Institute, vol. 93, no. 16, pp. 1246-1256.
Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N et al. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. Journal of the National Cancer Institute. 2001 Aug 15;93(16):1246-1256.
Smith, Justin S. ; Tachibana, Issei ; Passe, Sandra M. ; Huntley, Brenda K. ; Borell, Thomas J. ; Iturria, Nancy ; O'Fallon, Judith R. ; Schaefer, Paul L. ; Scheithauer, Bernd W. ; James, C. David ; Buckner, Jan Craig ; Jenkins, Robert Brian. / PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. In: Journal of the National Cancer Institute. 2001 ; Vol. 93, No. 16. pp. 1246-1256.
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abstract = "Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semi-quantitative polymerase chain reaction, and DNA sequenceing. All statistical test were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P<.001, respectively), and mutation of p53 was statisticaly significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma indentified PTEN (P = .002) and p53 (P = .012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performances score, and extent of tumor resection (hazard ratio = 4.34; 95{\%} confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of pro-longed survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.",
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T1 - PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme

AU - Smith, Justin S.

AU - Tachibana, Issei

AU - Passe, Sandra M.

AU - Huntley, Brenda K.

AU - Borell, Thomas J.

AU - Iturria, Nancy

AU - O'Fallon, Judith R.

AU - Schaefer, Paul L.

AU - Scheithauer, Bernd W.

AU - James, C. David

AU - Buckner, Jan Craig

AU - Jenkins, Robert Brian

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N2 - Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semi-quantitative polymerase chain reaction, and DNA sequenceing. All statistical test were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P<.001, respectively), and mutation of p53 was statisticaly significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma indentified PTEN (P = .002) and p53 (P = .012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performances score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of pro-longed survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

AB - Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semi-quantitative polymerase chain reaction, and DNA sequenceing. All statistical test were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P<.001, respectively), and mutation of p53 was statisticaly significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma indentified PTEN (P = .002) and p53 (P = .012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performances score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of pro-longed survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

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