PMID- 22742552
OWN - NLM
STAT- MEDLINE
DCOM- 20120914
LR  - 20220330
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 136
IP  - 7
DP  - 2012 Jul
TI  - Comparison of reverse transcription-polymerase chain reaction, 
      immunohistochemistry, and fluorescence in situ hybridization methodologies for 
      detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma 
      kinase fusion-positive non-small cell lung carcinoma: implications for optimal 
      clinical testing.
PG  - 796-803
LID - 10.5858/arpa.2011-0321-OA [doi]
AB  - CONTEXT: Echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma 
      kinase (EML4-ALK) gene fusions are detected in 3% to 13% of non-small cell lung 
      carcinomas. Accurate testing for detection of EML4-ALK fusions is essential for 
      appropriate therapy selection. OBJECTIVE: To compare reverse 
      transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and 
      fluorescence in situ hybridization (FISH) methodologies for detection of EML4-ALK 
      fusions. DESIGN: Forty-six pulmonary adenocarcinomas were selected with 
      enrichment for wild-type epidermal growth factor receptor (EGFR) status (wild 
      type, n  =  42; mutant, n  =  4). Specimens were tested by IHC (Dako; clone 
      ALK1), FISH (Abbott Molecular; LSI ALK break apart), and RT-PCR (variants 1 and 
      3a/b). RESULTS: EML4-ALK variant 3a/b was detectable by RT-PCR, FISH, and IHC in 
      4% (2 of 46) of specimens. Complete agreement among FISH and IHC reviewers was 
      obtained for variant 3a/b. No concordance existed among methodologies for the 
      detection of EML4-ALK variant 1. The RT-PCR method detected variant 1 in 20% (9 
      of 46) of specimens. Agreement among FISH viewers was poor for variant 1 because 
      only 11% (1/9) of specimens were scored as positive by all 3 viewers. The 
      sensitivity of IHC for detection of variant 1 was also poor because only 1 of 9 
      samples (11%) was scored as positive. Overall, the frequency of EML4-ALK variants 
      1 and 3a/b was 24% (11 of 46) in adenocarcinomas enriched for wild-type EGFR 
      status. One EML4-ALK variant 1 fusion was found to coexist with an EGFR exon 21 
      mutation. CONCLUSIONS: The FISH interpretation demonstrated great variability 
      among observers. The RT-PCR method was the most sensitive and least-subjective 
      methodology for detection of EML4-ALK fusions.
FAU - Wallander, Michelle L
AU  - Wallander ML
AD  - Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake 
      City, Utah, USA.
FAU - Geiersbach, Katherine B
AU  - Geiersbach KB
FAU - Tripp, Sheryl R
AU  - Tripp SR
FAU - Layfield, Lester J
AU  - Layfield LJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.4.21.- (EML4 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/metabolism/pathology
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/*diagnosis/genetics/metabolism/pathology
MH  - Microtubule-Associated Proteins/genetics/*metabolism
MH  - Oncogene Proteins, Fusion/genetics/*metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/*methods
MH  - Sensitivity and Specificity
MH  - Serine Endopeptidases/genetics/*metabolism
EDAT- 2012/06/30 06:00
MHDA- 2012/09/15 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/09/15 06:00 [medline]
AID - 10.5858/arpa.2011-0321-OA [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2012 Jul;136(7):796-803. doi: 10.5858/arpa.2011-0321-OA.