PMID- 29556606
OWN - NLM
STAT- MEDLINE
DCOM- 20180905
LR  - 20181202
IS  - 2066-8279 (Electronic)
IS  - 1220-0522 (Linking)
VI  - 58
IP  - 4
DP  - 2017
TI  - Preselection of EGFR mutations in non-small-cell lung cancer patients by 
      immunohistochemistry: comparison with DNA-sequencing, EGFR wild-type expression, 
      gene copy number gain and clinicopathological data.
PG  - 1175-1184
AB  - Targeting epidermal growth factor receptor (EGFR) in patients with non-small-cell 
      lung cancer (NSCLC) having EGFR mutations is associated with an improved overall 
      survival. The aim of this study is to verify, if EGFR mutations detected by 
      immunohistochemistry (IHC) is a convincing way to preselect patients for 
      DNA-sequencing and to figure out, the statistical association between EGFR 
      mutation, wild-type EGFR overexpression, gene copy number gain, which are the 
      main factors inducing EGFR tumorigenic activity and the clinicopathological data. 
      Two hundred sixteen tumor tissue samples of primarily chemotherapeutic naive 
      NSCLC patients were analyzed for EGFR mutations E746-A750del and L858R and 
      correlated with DNA-sequencing. Two hundred six of which were assessed by IHC, 
      using 6B6 and 43B2 specific antibodies followed by DNA-sequencing of positive 
      cases and 10 already genotyped tumor tissues were also included to investigate 
      debugging accuracy of IHC. In addition, EGFR wild-type overexpression was IHC 
      evaluated and EGFR gene copy number determination was performed by fluorescence 
      in situ hybridization (FISH). Forty-one/206 (19.9%) cases were positive for 
      mutated EGFR by IHC. Eight of them had EGFR mutations of exons 18-21 by 
      DNA-sequencing. Hit rate of 10 already genotyped NSCLC mutated cases was 90% by 
      IHC. Positive association was found between EGFR mutations determined by IHC and 
      both EGFR overexpression and increased gene copy number (p=0.002 and p<0.001, 
      respectively). Additionally, positive association was detected between EGFR 
      mutations, high tumor grade and clinical stage (p<0.001). IHC staining with 
      mutation specific antibodies was demonstrated as a possible useful screening test 
      to preselect patients for DNA-sequencing.
FAU - Gaber, Rania
AU  - Gaber R
AD  - Pathology of the University of Lubeck and the Research Center Borstel, Site 
      Borstel, Clinical and Experimental Pathology, Borstel, Airway Research Center 
      North (ARCN), German Center for Lung Research, Borstel, Germany; 
      tgoldmann@fz-borstel.de.
FAU - Watermann, Iris
AU  - Watermann I
FAU - Kugler, Christian
AU  - Kugler C
FAU - Vollmer, Ekkehard
AU  - Vollmer E
FAU - Perner, Sven
AU  - Perner S
FAU - Reck, Martin
AU  - Reck M
FAU - Goldmann, Torsten
AU  - Goldmann T
LA  - eng
PT  - Journal Article
PL  - Romania
TA  - Rom J Morphol Embryol
JT  - Romanian journal of morphology and embryology = Revue roumaine de morphologie et 
      embryologie
JID - 9112454
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*enzymology/*genetics/pathology
MH  - ErbB Receptors/*genetics/*metabolism
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - Lung Neoplasms/*enzymology/*genetics/pathology
MH  - Male
MH  - Mutation
MH  - Retrospective Studies
MH  - Sequence Analysis, DNA
EDAT- 2017/01/01 00:00
MHDA- 2018/09/06 06:00
CRDT- 2018/03/21 06:00
PHST- 2018/03/21 06:00 [entrez]
PHST- 2017/01/01 00:00 [pubmed]
PHST- 2018/09/06 06:00 [medline]
AID - 58041711751184 [pii]
PST - ppublish
SO  - Rom J Morphol Embryol. 2017;58(4):1175-1184.