PMID- 24878018
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20220311
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 138
IP  - 6
DP  - 2014 Jun
TI  - Immunohistochemistry, fluorescence in situ hybridization, and reverse 
      transcription-polymerase chain reaction for the detection of anaplastic lymphoma 
      kinase gene rearrangements in patients with non-small cell lung cancer: potential 
      advantages and methodologic pitfalls.
PG  - 794-802
LID - 10.5858/arpa.2012-0762-OA [doi]
AB  - CONTEXT: Echinoderm microtubule-associated protein-like 4 gene (EML4) and 
      anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of 
      tumorigenesis in approximately 3% to 5% of patients with non-small cell lung 
      cancer (NSCLC) and is associated with response to inhibition with crizotinib. 
      However, no complete agreement regarding the best diagnostic test for 
      identification of ALK rearrangements has been achieved yet. OBJECTIVE: To 
      investigate the concordance, sensitivity, and specificity of immunohistochemistry 
      (IHC), fluorescence in situ hybridization (FISH), and reverse 
      transcription-polymerase chain reaction (RT-PCR) for detection of ALK 
      rearrangements. DESIGN: Thirty-six prospectively tested patients with NSCLC who 
      had adenocarcinoma and 10 ALK-positive samples were included in the study. All 
      samples were tested by IHC (ALK1 clone, 5A4 clone, D5F3 clone), FISH (LSI ALK 
      Break Apart and ALK FISH Probe), and multiplexed RT-PCR. RESULTS: 
      Immunohistochemistry staining was successful in all samples.. Clone D5F3 showed 
      the best sensitivity and specificity of 100%; clones ALK1 and 5A4 showed 
      sensitivities of 91% with specificity of 100%. Both FISH probes showed 
      concordance with sensitivity and specificity of 100%. Hybridization and RT-PCR 
      were successful in 98% and 93.4% of samples, respectively, with sensitivity of 
      88% and specificity of 100%. Frequent artifacts leading to misinterpretation were 
      observed with all 3 methodologies. CONCLUSIONS: All 3 methodologies showed good 
      sensitivity, specificity, and concordance, when artifacts were characterized and 
      excluded. However, all ambiguous cases have to be confirmed as ALK rearranged by 
      at least 2 of the 3 methods.
FAU - Demidova, Irina
AU  - Demidova I
AD  - From the Laboratory of Molecular Diagnostics (Drs Demidova and Gagarin and Mr 
      Barinov), the Departments of Pathology (Drs Savelov and Grinevitch), Chemotherapy 
      (Dr Stroiakovaski), and Thoracic Surgery (Dr Popov), Moscow Oncological Hospital 
      62, Moscow, Russia; the Departments of Thoracic Oncology (Dr Laktionov) and 
      Chemotherapy (Dr Gutorov), N. N. Blokhin Russian Cancer Research Center of 
      Russian Academy of Medical Sciences, Moscow, Russia; the Department of Radiology, 
      N. N. Burdenko Central Military Hospital, Moscow, Russia (Dr Smolin); the 
      Laboratory of Cytogenetics and Molecular Genetics, Russian Federal Center for 
      Pediatric Hematology, Oncology and Immunology, Moscow, Russia (Ms Olshanskaya); 
      and the Laboratory of Cytogenetics, Russian Scientific Center for Hematology, 
      Moscow, Russia (Ms Obukhova).
FAU - Barinov, Aleksei
AU  - Barinov A
FAU - Savelov, Nikita
AU  - Savelov N
FAU - Gagarin, Ilia
AU  - Gagarin I
FAU - Grinevitch, Viacheslav
AU  - Grinevitch V
FAU - Stroiakovaski, Daniil
AU  - Stroiakovaski D
FAU - Popov, Mikhail
AU  - Popov M
FAU - Laktionov, Konstantin
AU  - Laktionov K
FAU - Gutorov, Sergei
AU  - Gutorov S
FAU - Smolin, Alexei
AU  - Smolin A
FAU - Olshanskaya, Yulia
AU  - Olshanskaya Y
FAU - Obukhova, Tatiana
AU  - Obukhova T
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (DNA, Neoplasm)
RN  - 0 (EML4-ALK fusion protein, human)
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)
SB  - IM
MH  - Adenocarcinoma/genetics/metabolism/pathology
MH  - Adenocarcinoma of Lung
MH  - Anaplastic Lymphoma Kinase
MH  - Base Sequence
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*metabolism/pathology
MH  - DNA, Neoplasm/genetics
MH  - *Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry/statistics & numerical data
MH  - In Situ Hybridization, Fluorescence/statistics & numerical data
MH  - Lung Neoplasms/*genetics/*metabolism/pathology
MH  - Oncogene Proteins, Fusion/genetics
MH  - Prospective Studies
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data
EDAT- 2014/06/01 06:00
MHDA- 2014/08/15 06:00
CRDT- 2014/06/01 06:00
PHST- 2014/06/01 06:00 [entrez]
PHST- 2014/06/01 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 10.5858/arpa.2012-0762-OA [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2014 Jun;138(6):794-802. doi: 10.5858/arpa.2012-0762-OA.