Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance

Kenneth D. Aldape, Karla Ballman, Alfred Furth, Jan Craig Buckner, Caterina Giannini, Peter C. Burger, Bernd W. Scheithauer, Robert Brian Jenkins, C. David James

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.

Original languageEnglish (US)
Pages (from-to)700-707
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number7
StatePublished - Jul 2004

Fingerprint

Astrocytoma
Glioblastoma
Neoplasms
Paraffin
Formaldehyde
Polymerase Chain Reaction
Survival
Survival Analysis
epidermal growth factor receptor VIII
Clinical Trials
RNA
Proteins

Keywords

  • Amplification
  • Astrocytoma
  • EGFRvIII
  • Glioblastoma
  • Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. / Aldape, Kenneth D.; Ballman, Karla; Furth, Alfred; Buckner, Jan Craig; Giannini, Caterina; Burger, Peter C.; Scheithauer, Bernd W.; Jenkins, Robert Brian; James, C. David.

In: Journal of Neuropathology and Experimental Neurology, Vol. 63, No. 7, 07.2004, p. 700-707.

Research output: Contribution to journalArticle

@article{3e9ab4552bf94cf799e0d633c094381e,
title = "Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance",
abstract = "The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3{\%}) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1{\%}). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4{\%}) and in 6 of 49 cases without EGFR amplification (12.2{\%}). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.",
keywords = "Amplification, Astrocytoma, EGFRvIII, Glioblastoma, Immunohistochemistry",
author = "Aldape, {Kenneth D.} and Karla Ballman and Alfred Furth and Buckner, {Jan Craig} and Caterina Giannini and Burger, {Peter C.} and Scheithauer, {Bernd W.} and Jenkins, {Robert Brian} and James, {C. David}",
year = "2004",
month = "7",
language = "English (US)",
volume = "63",
pages = "700--707",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance

AU - Aldape, Kenneth D.

AU - Ballman, Karla

AU - Furth, Alfred

AU - Buckner, Jan Craig

AU - Giannini, Caterina

AU - Burger, Peter C.

AU - Scheithauer, Bernd W.

AU - Jenkins, Robert Brian

AU - James, C. David

PY - 2004/7

Y1 - 2004/7

N2 - The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.

AB - The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.

KW - Amplification

KW - Astrocytoma

KW - EGFRvIII

KW - Glioblastoma

KW - Immunohistochemistry

UR - http://www.scopus.com/inward/record.url?scp=3042757984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042757984&partnerID=8YFLogxK

M3 - Article

C2 - 15290895

AN - SCOPUS:3042757984

VL - 63

SP - 700

EP - 707

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 7

ER -