Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis.
c-Kit receptor (CD117) is expressed by erythroid, megakaryocytic, and myeloid precursors and mature mast cells and has been reported to be expressed in CD30+ lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma. Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. In view of the possible use of imatinib as experimental therapy for patients with c-kit-positive tumors, we assessed c-kit expression in CD30+ cell lines and lymphomas. The cell lines were assessed using multiple methods (RT-PCR, flow cytometry, and Western blot). c-Kit expression was also immunohistochemically assessed in 168 CD30+ lymphomas including 87 classical Hodgkin's disease, 63 anaplastic large-cell lymphoma, and 15 cutaneous anaplastic large-cell lymphoma. We also studied 18 cases of lymphomatoid papulosis, a CD30+ lesion closely related to cutaneous anaplastic large-cell lymphoma. Neither c-kit mRNA nor protein was detected in any of the cell lines assessed. Furthermore, treatment with imatinib did not inhibit proliferation of cell lines in vitro. Using immunohistochemistry, only one of 183 (0.5%) lesions was positive for c-kit, the positive case being an ALK-negative anaplastic large-cell lymphoma. Our data demonstrate that expression of c-kit receptor is exceedingly rare among CD30+ lymphomas and lymphomatoid papulosis, suggesting that c-kit receptor is unlikely to be an appropriate target for therapeutic options such as imatinib in patients with these tumors.
Rassidakis
George Z
GZ
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Georgakis
Georgios V
GV
Oyarzo
Mauricio
M
Younes
Anas
A
Medeiros
L Jeffrey
LJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000032:analysis; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017731:Lymphomatoid Papulosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D001549:Benzamides; D017730:Ki-1 Antigen; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit