Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era

Christine Carico, Miriam A Nuno, Debraj Mukherjee, Adam Elramsisy, Jocelynn Dantis, Jethro Hu, Jeremy Rudnick, John S. Yu, Keith L. Black, Serguei I. Bannykh, Chirag G. Patil

Research output: Contribution to journalReview article

45 Citations (Scopus)

Abstract

Introduction: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Methods: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival. Results: Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p =. 71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p =. 01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p =. 04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p =. 22). Conclusions: Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.

Original languageEnglish (US)
Article numbere33684
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 29 2012
Externally publishedYes

Fingerprint

temozolomide
Glioblastoma
Survival
Karnofsky Performance Status
Genes
erbB-1 Genes
hazard characterization
tumor suppressor genes
phosphatidylinositol 3-kinase
resection
Tumor Suppressor Genes
Phosphatidylinositol 3-Kinases
carcinogenesis
multivariate analysis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era. / Carico, Christine; Nuno, Miriam A; Mukherjee, Debraj; Elramsisy, Adam; Dantis, Jocelynn; Hu, Jethro; Rudnick, Jeremy; Yu, John S.; Black, Keith L.; Bannykh, Serguei I.; Patil, Chirag G.

In: PLoS One, Vol. 7, No. 3, e33684, 29.03.2012.

Research output: Contribution to journalReview article

Carico, C, Nuno, MA, Mukherjee, D, Elramsisy, A, Dantis, J, Hu, J, Rudnick, J, Yu, JS, Black, KL, Bannykh, SI & Patil, CG 2012, 'Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era', PLoS One, vol. 7, no. 3, e33684. https://doi.org/10.1371/journal.pone.0033684
Carico, Christine ; Nuno, Miriam A ; Mukherjee, Debraj ; Elramsisy, Adam ; Dantis, Jocelynn ; Hu, Jethro ; Rudnick, Jeremy ; Yu, John S. ; Black, Keith L. ; Bannykh, Serguei I. ; Patil, Chirag G. / Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era. In: PLoS One. 2012 ; Vol. 7, No. 3.
@article{91caa6f8e1cd46738e27dc62ae5318f6,
title = "Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era",
abstract = "Introduction: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Methods: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival. Results: Sixty-five percent of patients were men with median age of 63 years, and 70{\%} had KPS≥80. Most patients (81{\%}) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47{\%}) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95{\%} CI: 15.0-22.5). Median survival of 20.0 months (95{\%} CI: 15.0-25.5) and 18.2 months (95{\%} CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p =. 71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8{\%} vs. 47.8{\%}, p =. 01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p =. 04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p =. 22). Conclusions: Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.",
author = "Christine Carico and Nuno, {Miriam A} and Debraj Mukherjee and Adam Elramsisy and Jocelynn Dantis and Jethro Hu and Jeremy Rudnick and Yu, {John S.} and Black, {Keith L.} and Bannykh, {Serguei I.} and Patil, {Chirag G.}",
year = "2012",
month = "3",
day = "29",
doi = "10.1371/journal.pone.0033684",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era

AU - Carico, Christine

AU - Nuno, Miriam A

AU - Mukherjee, Debraj

AU - Elramsisy, Adam

AU - Dantis, Jocelynn

AU - Hu, Jethro

AU - Rudnick, Jeremy

AU - Yu, John S.

AU - Black, Keith L.

AU - Bannykh, Serguei I.

AU - Patil, Chirag G.

PY - 2012/3/29

Y1 - 2012/3/29

N2 - Introduction: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Methods: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival. Results: Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p =. 71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p =. 01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p =. 04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p =. 22). Conclusions: Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.

AB - Introduction: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Methods: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival. Results: Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p =. 71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p =. 01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p =. 04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p =. 22). Conclusions: Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.

UR - http://www.scopus.com/inward/record.url?scp=84859091170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859091170&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0033684

DO - 10.1371/journal.pone.0033684

M3 - Review article

C2 - 22479427

AN - SCOPUS:84859091170

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e33684

ER -