Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood.
BACKGROUND
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase inappropriately expressed in lymphoid tissue involved by CD30+ anaplastic large-cell lymphoma (ALCL) with the translocation t(2;5)(p23;q35)(, which juxtaposes the nucleophosmin gene (NPM) with that encoding ALK, resulting in a hybrid (NPM-ALK) message.


METHODS
A polyclonal antibody against residues of the kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL) and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase method.


RESULTS
Nineteen of 20 CD30+ cases (the majority exhibiting anaplastic morphology) labeled with anti-ALK 11, and 5/28 CD30- cases were also ALK+ (3 T cells, 1 null cell, and 1 B cell). Sixteen of 17 B-cell pediatric LCLs were negative, as were 6/6 cases of Hodgkin's disease and 7/7 cases of adult B-cell lymphoma. In pediatric LCLs with adequate follow-up (24/44 ALK+), there was no significant association between ALK expression and two-year event-free survival, similar to the finding reported previously for CD30 expression in these cases.


CONCLUSIONS
We conclude that the majority of pediatric CD30+ ALCLs show ALK overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK fusion, but that the clinical significance of this entity remains unproven.
Hutchison
R E
RE
State University of New York, Health Science Center, Syracuse, USA.
Banki
K
K
Shuster
J J
JJ
Barrett
D
D
Dieck
C
C
Berard
C W
CW
Murphy
S B
SB
Link
M P
MP
Pick
T E
TE
Laver
J
J
Schwenn
M
M
Mathew
P
P
Morris
S W
SW
D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000906:Antibodies; D002648:Child; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D016612:Paraffin Embedding; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases
D000906:Antibodies; D017730:Ki-1 Antigen; D009363:Neoplasm Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases