MIC2 analysis in pediatric lymphomas and leukemias

Abstract

Monoclonal antibodies to the glycoprotein product of the MIC2 gene strongly and reliably stain primitive neuroectodermal tumors and Ewing's sarcomas, and are negative in neuroblastomas and most rhabdomyosarcomas. Therefore, these antibodies are helpful in the diagnosis of small round cell tumors of childhood (SRCT). Lymphomas also are in the differential diagnosis of SRCT, but few have been studied with respect to MIC2 protein expression. In the present study we used the 12E7 antibody to assess MIC2 expression in 82 pediatric non-Hodgkin's lymphomas. Forty lymphoblastic, 22 small noncleaved, and 20 large cell lymphomas were studied. Strong immunoreactivity was found in 37 of the 40 (93%) lymphoblastic lymphomas, whereas only one of the 22 (5%) small noncleaved lymphomas was 12E7 positive. Four of the 20 (20%) large cell lymphomas also were immunoreactive. Three 12E7+ lymphoblastic lymphomas were primary in bone and were of B-progenitor lineage; Ewing's sarcoma was included in the initial differential diagnosis of these cases. Evaluation of 125 pediatric acute lymphocytic leukemia (ALL) cases for MIC2 expression showed similar results, with all 36 T-cell ALLs showing strong expression, one of eight B-cell (Burkitt-like) ALLs showing 12E7 expression, and 62 of 81 B-progenitor ALLs showing 12E7 positivity. We conclude that among the SRCTs, MIC2 expression is not limited to Ewing's sarcoma and primitive neuroectodermal tumors, but also shows strong and reliable expression in lymphoblastic lymphomas and related leukemias. MIC2 analysis continues to be helpful in the diagnosis of SRCT, provided that a panel of antibodies is used. In addition, the possibility that MIC2 analysis may aid in the distinction of lymphoblastic lymphomas from small noncleaved lymphomas needs to be further addressed.