ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung.
BACKGROUND
The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such molecular predictive test.


METHODS
A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A.


RESULTS
Squamous differentiation was confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an ALK rearrangement on fluorescence in situ hybridization analysis.


CONCLUSIONS
ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.
Departments of *Pathology and Diagnostics, †Surgery and Oncology, Medical Oncology Unit, University and Hospital Trust of Verona, Verona, Italy; ‡Cytomolecular Lab, Hartmann Institute, University of Helsinki, Finland; §Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino, Italy; and ‖ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy.
Anna
A
Caliò
Alessia
A
Nottegar
Eliana
E
Gilioli
Emilio
E
Bria
Sara
S
Pilotto
Umberto
U
Peretti
Stefania
S
Kinspergher
Francesca
F
Simionato
Serena
S
Pedron
Sakari
S
Knuutila
Giampaolo
G
Tortora
Albino
A
Eccher
Antonio
A
Santo
Luca
L
Tondulli
Giorgio
G
Inghirami
Fabrizio
F
Tabbò
Guido
G
Martignoni
Marco
M
Chilosi
Aldo
A
Scarpa
Matteo
M
Brunelli
D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000032:analysis; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
C522504:EML4-ALK fusion protein, human; D053555:Keratin-5; D053553:Keratin-6; D053552:Keratin-7; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C115051:TP63 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human