PMID- 9307304
OWN - NLM
STAT- MEDLINE
DCOM- 19971020
LR  - 20220825
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 18
DP  - 1997 Sep 15
TI  - Cell surface localization and density of the tumor-associated variant of the 
      epidermal growth factor receptor, EGFRvIII.
PG  - 4130-40
AB  - The potential of therapeutic targeting of tumor cell surface epidermal growth 
      factor receptors (EGFRs) by modified ligands or specific antibodies has been 
      limited by the normal tissue distribution of the receptor. The identification and 
      characterization of a variant of this receptor, EGFRvIII, which is not expressed 
      in normal tissues but has been described in gliomas, non-small cell lung 
      carcinomas, and breast carcinomas, has provided a highly specific, internalizing 
      target for antibody-mediated approaches. To determine the feasibility of 
      immunotargeting EGFRvIII, we have assessed the qualitative distribution and 
      quantitative expression at both the population and cellular levels of EGFRvIII in 
      21 biopsy samples of human gliomas by indirect analytical and quantitative flow 
      cytometry and by immunohistochemical assay of frozen and formalin-fixed tissue. 
      Consistent with previous reports, 50% of gliomas tested (1 of 2 anaplastic 
      astrocytomas, 7 of 12 glioblastoma multiforme, and 2 of 6 oligodendrogliomas) 
      expressed EGFRvIII, as determined by a minimum of 2 separate assays. Minimum 
      estimates of the proportion of positive tumor cells in these populations ranged 
      from 37-86%; in four of five cases in which quantitation of the EGFRvIII 
      density/cell was performed, values of 2.7-6.8 x 10(5) were obtained with 
      monoclonal antibody (mAb) L8A4 (EGFRvIII specific), levels consistent with 
      successful in vivo immunotargeting. Confocal microscopic analysis confirmed that 
      the subcellular localization of EGFRvIII was identical to that described for 
      EGFR: predominant cell membrane expression, with some perinuclear distribution 
      suggestive of localization to the Golgi region. Neither EGFR nor EGFRvIII was 
      found within the nucleus. This study establishes for the first time that 
      approximately 50% of human glioma biopsies contain cell populations expressing a 
      sufficient number of membrane-expressed EGFRvIIIs to mediate specific 
      anti-EGFRvIII mAb localization. Coupled with previous demonstrations of the rapid 
      internalization of specific mAb-EGFRvIII complexes and the susceptibility of the 
      targeted cells to isotope or toxin-mediated cytotoxicity, this study establishes 
      the validity of targeting EGFRvIII for therapy of mutant receptor-positive 
      gliomas, breast carcinomas, and non-small cell lung carcinomas.
FAU - Wikstrand, C J
AU  - Wikstrand CJ
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - McLendon, R E
AU  - McLendon RE
FAU - Friedman, A H
AU  - Friedman AH
FAU - Bigner, D D
AU  - Bigner DD
LA  - eng
GR  - CA11898/CA/NCI NIH HHS/United States
GR  - NS20023/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigen-Antibody Complex)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Antigen-Antibody Complex/metabolism
MH  - Biopsy
MH  - Cell Compartmentation
MH  - Cell Membrane/metabolism
MH  - Central Nervous System Neoplasms/*metabolism/pathology
MH  - Endocytosis
MH  - ErbB Receptors/*metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Glioma/*metabolism/pathology
MH  - Humans
MH  - Mice
MH  - Microscopy, Confocal
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1997/10/27 00:00
MHDA- 1997/10/27 00:01
CRDT- 1997/10/27 00:00
PHST- 1997/10/27 00:00 [pubmed]
PHST- 1997/10/27 00:01 [medline]
PHST- 1997/10/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Sep 15;57(18):4130-40.