Lack of HER-2/neu Overexpression in Non-Hodgkin's Lymphoma

Objectives: The HER-2/neu oncogene is overexpressed in many types of cancer and especially in 25% to 30% of breast cancers. Single reports mention HER-2/neu positivity in hematological malignancies like Hodgkins's disease and even diffuse large-cell lymphoma. Objective. To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin®) in the treatment of non-Hodgkin's lymphoma. Materials and Methods: Serum samples from 87 consecutive unselected patients with non-Hodgkin's lymphoma were retrospectively retrieved from a serum bank and tested for the shed antigen of HER-2/neu using the Oncogene Science® ELISA assay (Cambridge, MA, USA). From those lymphoma patients, the paraffin-embedded lymph-node specimens of 25 cases with diffuse large-cell lymphoma were stained with the HER-2/neu DAKO HercepTest®. Results: In 87 lymphoma patients, the serum level of HER-2/neu ranged from 3.6 to 244.1 ng/ml (median 8.0 ng/ml). Only 2 patients showed a marginal or increased HER-2/neu level with 15 ng/ml (which is the upper limit of normal) and 244.1 ng/ml, respectively. No patient with diffuse large-cell lymphoma showed HER-2/neu overexpression by immunhistochemistry of the lymph node. The paraffin block of the one patient with a very high HER-2/neu serum level was also stained for HER-2/neu overexpression. In this patient, suffering from a high-grade T-cell non-Hodgkin's lymphoma, no staining could be found. Conclusion: HER-2/neu is not overexpressed in non-Hodgkin's lymphoma and especially not in diffuse large-cell lymphoma, using a standardized immunochemistry technique with complementary serum testing. Thus, specific anti-HER-2/neu-targeted therapy should play no role in the treatment of non-Hodgkin's lymphoma.