PMID- 25099128
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20181202
IS  - 1934-6638 (Electronic)
IS  - 1934-662X (Linking)
VI  - 122
IP  - 11
DP  - 2014 Nov
TI  - Cytology specimens offer an effective alternative to formalin-fixed tissue as 
      demonstrated by novel automated detection for ALK break-apart FISH testing and 
      immunohistochemistry in lung adenocarcinoma.
PG  - 810-21
LID - 10.1002/cncy.21467 [doi]
AB  - BACKGROUND: Minimally invasive sampling by cytology or core needle biopsy often 
      provides an initial diagnosis for treatment in patients with lung nodules. From 
      these limited specimens, multiple molecular studies are frequently requested. 
      Current guidelines from the US Food and Drug Administration recommend using 
      formalin-fixed paraffin-embedded tissue sections for the detection of anaplastic 
      lymphoma kinase (ALK) gene rearrangement by fluorescence in situ hybridization 
      (FISH). The authors compared alcohol-fixed and formalin-fixed cytology specimens 
      using a novel automated detection for ALK rearrangements by FISH and 
      immunohistochemistry (IHC). METHODS: ALK FISH testing was performed on 129 lung 
      adenocarcinomas from 71 cytology cases and 58 biopsy/resection specimens using 
      Papanicolaou staining with integrated cytomorphology. IHC with the ALK D5F3 
      antibody was performed on cases with residual material (88 of 129 cases). 
      RESULTS: The mean age of the patients was 66 years; there were 62 women and 67 
      men. ALK gene rearrangement was present in 4% of cytology specimens (3 of 71 
      specimens) and 7% of surgical specimens (4 of 58 specimens). FISH in 13 cases was 
      technically unsuccessful. Of the 7 FISH-positive cases, only 2 cytology cases 
      (4%) and 2 surgical cases (6%) were found to be positive with the ALK antibody, 
      demonstrating 80% concordance. The one case found to be negative for ALK by IHC 
      demonstrated a variant rearrangement of the ALK 2p23 gene locus by FISH. 
      CONCLUSIONS: The results of the current study validate the usefulness of 
      alcohol-fixed and/or formalin-fixed cytology specimens for ALK rearrangement by a 
      novel automated FISH method. IHC using the D5F3 antibody for ALK is specific in 
      this limited cohort. The authors also demonstrated that alcohol-fixed cytology 
      specimens can be used for ALK rearrangement by automated FISH, alone or in 
      conjunction with IHC.
CI  - (c) 2014 American Cancer Society.
FAU - Rosenblum, Frida
AU  - Rosenblum F
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Hutchinson, Lloyd M
AU  - Hutchinson LM
FAU - Garver, Joann
AU  - Garver J
FAU - Woda, Bruce
AU  - Woda B
FAU - Cosar, Ediz
AU  - Cosar E
FAU - Kurian, Elizabeth M
AU  - Kurian EM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140805
PL  - United States
TA  - Cancer Cytopathol
JT  - Cancer cytopathology
JID - 101499453
RN  - 0 (Alcohols)
RN  - 0 (Fixatives)
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/genetics/metabolism
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alcohols/chemistry
MH  - Anaplastic Lymphoma Kinase
MH  - Cytodiagnosis/methods
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Fixatives/*chemistry
MH  - Formaldehyde/chemistry
MH  - Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/*diagnosis/genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Papanicolaou Test/methods
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Tissue Fixation/methods
MH  - Young Adult
MH  - ras Proteins/genetics
OTO - NOTNLM
OT  - ALK immunohistochemistry
OT  - anaplastic lymphoma kinase (ALK)
OT  - crizotinib
OT  - fluorescence in situ hybridization (FISH)
OT  - lung adenocarcinoma
OT  - lung cytology
EDAT- 2014/08/08 06:00
MHDA- 2015/01/27 06:00
CRDT- 2014/08/08 06:00
PHST- 2014/03/13 00:00 [received]
PHST- 2014/06/24 00:00 [revised]
PHST- 2014/07/07 00:00 [accepted]
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
AID - 10.1002/cncy.21467 [doi]
PST - ppublish
SO  - Cancer Cytopathol. 2014 Nov;122(11):810-21. doi: 10.1002/cncy.21467. Epub 2014 
      Aug 5.