The use of stained cytologic direct smears forALKgene rearrangement analysis of lung adenocarcinoma

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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.


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.


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.


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. Cancer (Cancer Cytopathol) 2013;121:489-99. © 2013 American Cancer Society.

The authors demonstrate that cytologic direct smear preparations of lung adenocarcinoma can be effectively used for the analysis of anaplastic lymphoma kinase (ALK) rearrangement by fluorescence in situ hybridization. This approach can complement the use of cell blocks for such testing, especially for situations in which insufficient cell block cellularity is encountered or anticipated.

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