Fusion of a Kinase Gene, <i>ALK</i> , to a Nucleolar Protein Gene, <i>NPM</i> , in Non-Hodgkin's LymphomaThe 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Detection of Anaplastic Lymphoma Kinase (ALK) and Nucleolar Protein Nucleophosmin (NPM)-ALK Proteins in Normal and Neoplastic Cells With the Monoclonal Antibody ALK1The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the production of the nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) protein. This report describes an immunocytochemical study of the distribution of ALK and NPM-ALK proteins using a new monoclonal antibody, ALK1, that recognizes a formalin resistant epitope in both the 80-kD NPM-ALK chimeric and the 200-kD normal human ALK proteins. Cytoplasmic and nuclear labeling was seen in the t(2;5)+ SU-DHL-1 and Karpas 299 cell lines. Normal ALK protein expression was restricted to the central nervous system (in scattered neurons, glial cells, and endothelial cells). Two hundred and thirty-nine cases of lymphoma and 80 nonhematopoietic tumors were immunostained. Antibody ALK1 labeled 53.4% (39 of 73 cases) of CD30+ ALCL. A case of ALCL with a t(1;2) translocation was ALK1+. Three cases of CD30- ALCL with prominent nucleoli showed a unique pattern of coarse granular cytoplasmic labeling. All other tumors, including Hodgkin's disease and lymphomatoid papulosis, were ALK1-. These results indicate that reliable immunostaining of routine biopsy material for NPM-ALK and ALK proteins is feasible. Such analysis is of diagnostic importance, especially because t(2;5)+ ALCL cases have a good prognosis with appropriate treatment.
Anaplastic Lymphoma Kinase (ALK) Expression in the Inflammatory Myofibroblastic TumorJames R. Cook, Louis P. Dehner, Margaret H. Collins et al.|The American Journal of Surgical Pathology|2001 Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal neoplasm with a variable histologic appearance that may mimic other spindle cell processes, particularly nodular fasciitis, desmoid tumor, and in intra-abdominal locations, gastrointestinal stromal tumor. Recently, gene fusions involving ALK at chromosome 2p23 have been described in IMTs. The resultant ALK protein overexpression in the myofibroblastic component of these tumors is detectable by immunohistochemistry. We examined 73 IMTs, 20 cases of nodular fasciitis, 15 desmoid fibromatoses, and 15 gastrointestinal stromal tumors by immunohistochemistry using ALK-11, a rabbit polyclonal antibody that recognizes the C-terminus of the protein. ALK positivity was detected in 44 of 73 (60%) IMTs. All cases of nodular fasciitis, desmoid fibromatosis, and gastrointestinal stromal tumors were ALK negative (p < 0.001). These findings demonstrate that ALK positivity is common in IMTs, and immunohistochemistry using anti-ALK antibodies can be helpful in the differential diagnosis of these neoplasms. In addition, anti-ALK staining seems to correlate with those IMTs that have the typical tri-patterned histologic appearance and clinical presentation, providing additional support to the premise that IMT is a distinctive clinicopathologic entity within the broad category of inflammatory pseudotumors.