title: Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.
abstract: BACKGROUND
  Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours.
  
  
  METHODS
  We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies.
  
  
  RESULTS
  Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4.
  
  
  CONCLUSIONS
  Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, CHU Nice, and Medical School, Nice Sophia University, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Hofman
authors.forename: M
authors.initials: M
authors.lastname: Ilie
authors.forename: V
authors.initials: V
authors.lastname: Hofman
authors.forename: S
authors.initials: S
authors.lastname: Roux
authors.forename: A
authors.initials: A
authors.lastname: Valent
authors.forename: A
authors.initials: A
authors.lastname: Bernheim
authors.forename: M
authors.initials: M
authors.lastname: Alifano
authors.forename: F
authors.initials: F
authors.lastname: Leroy-Ladurie
authors.forename: F
authors.initials: F
authors.lastname: Vaylet
authors.forename: I
authors.initials: I
authors.lastname: Rouquette
authors.forename: P
authors.initials: P
authors.lastname: Validire
authors.forename: M
authors.initials: M
authors.lastname: Beau-Faller
authors.forename: L
authors.initials: L
authors.lastname: Lacroix
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
authors.forename: P
authors.initials: P
authors.lastname: Fouret
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012907:Smoking; D018631:ras Proteins / Q000235:genetics
chemical_list: C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins