Patterns of ALK expression in different human cancer types.
OBJECTIVE
Oncogenic gene fusions involving the anaplastic lymphoma kinase (ALK) tyrosine kinase have been identified in several haematopoietic and sporadically also in solid tumour types. Preliminary results from clinical trials suggest that patients with ALK fusion positive cancers might optimally benefit from the tyrosine kinase inhibitor crizotinib, but a comprehensive analysis of solid tumour types for ALK fusion and fusion associated expression is lacking.


METHODS
In order to identify human solid cancers carrying ALK alterations, we performed real-time PCR screening of 1000 tumour samples representing 29 different tumour entities. ALK-positive samples were then transferred into a tissue microarray format and subjected to ALK break-apart fluorescence in situ hybridisation (FISH) analysis and ALK immunohistochemistry (IHC) analysis.


RESULTS
ALK expression was detected by real-time PCR in 260 of 896 (29%) interpretable tumour samples. FISH analysis was successful in 189 of 260 arrayed cancers but did not detect ALK rearrangement. There was also no ALK expression detectable by IHC.


CONCLUSIONS
Different levels of ALK expression can be found in various cancer types using sensitive methods like real-time PCR. However, such low-level expression is independent from oncogenic ALK fusions and cannot be detected with less-sensitive methods like IHC. ALK fusion is a rare event in human solid cancers.
Martini-Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Pierre
P
Tennstedt
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Gundula
G
Strobel
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Charlotte
C
Bölch
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Tobias
T
Grob
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sarah
S
Minner
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sawinee
S
Masser
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ronald
R
Simon
D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009369:Neoplasms / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
CANCER GENETICS; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDISATION; MOLECULAR PATHOLOGY