PMID- 23536384
OWN - NLM
STAT- MEDLINE
DCOM- 20131114
LR  - 20181202
IS  - 1934-6638 (Electronic)
IS  - 1934-662X (Linking)
VI  - 121
IP  - 9
DP  - 2013 Sep
TI  - The use of stained cytologic direct smears for ALK gene rearrangement analysis of 
      lung adenocarcinoma.
PG  - 489-99
LID - 10.1002/cncy.21286 [doi]
AB  - BACKGROUND: Rearrangements involving the anaplastic lymphoma kinase (ALK) gene 
      are present in approximately 5% of lung adenocarcinomas. Crizotinib is approved 
      for the treatment of lung adenocarcinomas harboring ALK rearrangements. Patients 
      with advanced stage lung cancer are not candidates for surgical resection of 
      their primary tumors. For these patients, cytologic specimens often represent the 
      only diagnostic tissue available. Cell blocks (CBs) are routinely used for 
      molecular studies; however, insufficient CB cellularity can impede the 
      performance of these assays. METHODS: Thirty-two cytology cases of lung 
      adenocarcinomas were analyzed by fluorescence in situ hybridization (FISH) for 
      ALK rearrangements. Diff-Quik-stained smears were examined to identify tumor 
      cell-enriched areas that were marked using a diamond-tipped scribe. Paired ALK 
      rearrangement FISH was performed using smears and CBs in each case. RESULTS: An 
      ALK rearrangement was detected on direct smears and CB sections in 5 (16%) and 4 
      (13%), respectively, of the 32 cases studied. Concordant FISH results for smears 
      and CBs were observed in 31 (97%) of 32 cases. In the 1 discordant case, an ALK 
      rearrangement was detected on the direct smear but not in the CB. Reverse 
      transcriptase-polymerase chain reaction analysis of this CB revealed the presence 
      of an EML4-ALK rearrangement, thereby confirming a false-negative FISH result in 
      the CB. CONCLUSIONS: Stained cytologic direct smears can be effectively used for 
      ALK rearrangement analysis by FISH. This approach represents a useful safeguard 
      when insufficient CB cellularity is encountered and could prevent delays in 
      treatment in this era of precision medicine.
CI  - Copyright (c) 2013 American Cancer Society.
FAU - Betz, Bryan L
AU  - Betz BL
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, 
      Michigan.
FAU - Dixon, Catherine A
AU  - Dixon CA
FAU - Weigelin, Helmut C
AU  - Weigelin HC
FAU - Knoepp, Stewart M
AU  - Knoepp SM
FAU - Roh, Michael H
AU  - Roh MH
LA  - eng
PT  - Journal Article
DEP - 20130327
PL  - United States
TA  - Cancer Cytopathol
JT  - Cancer cytopathology
JID - 101499453
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA, Messenger)
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/diagnosis/*genetics
MH  - Anaplastic Lymphoma Kinase
MH  - Biomarkers, Tumor/*genetics
MH  - *Cytodiagnosis
MH  - *Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/diagnosis/*genetics
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Prognosis
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
OTO - NOTNLM
OT  - adenocarcinoma
OT  - anaplastic lymphoma kinase (ALK) rearrangement
OT  - cytology
OT  - direct smear
OT  - fine-needle aspiration
OT  - fluorescence in situ hybridization
OT  - lung cancer
OT  - non-small cell lung cancer
OT  - precision medicine
EDAT- 2013/03/29 06:00
MHDA- 2013/11/15 06:00
CRDT- 2013/03/29 06:00
PHST- 2012/12/23 00:00 [received]
PHST- 2013/01/29 00:00 [revised]
PHST- 2013/02/04 00:00 [accepted]
PHST- 2013/03/29 06:00 [entrez]
PHST- 2013/03/29 06:00 [pubmed]
PHST- 2013/11/15 06:00 [medline]
AID - 10.1002/cncy.21286 [doi]
PST - ppublish
SO  - Cancer Cytopathol. 2013 Sep;121(9):489-99. doi: 10.1002/cncy.21286. Epub 2013 Mar 
      27.