Expression of Disialoganglioside GD2 in Neuroblastomas of Patients Treated with Immunotherapy
Tatjana Terzic, Pierre Teira, Sonia Cournoyer, Michel Peuchmaur, Herve Sartelet. Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada; Hopital Universitaire Robert-Debre, Paris, France
Background: Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of the most aggressive pediatric cancers with a tendency for widespread dissemination, relapse and a poor long term survival, despite intensive multimodal treatments. Recent use of immunotherapy (a chimeric human-murine monoclonal antibody ch14.18 directed against a tumor-associated antigen GD2, a disialoganglioside) to treat minimal residual disease has shown improvement in event-free and overall survival of high-risk neuroblastomas. However, some patients are resistant to immunotherapy. Therefore, the aim of the study was to analyze GD2 expression in neuroblastomas and see if the resistance to immunotherapy could be explained by the poor expression of GD2.
Design: We realized an immunohistochemical study on 140 cases of neuroblastomas included in TMAs and on 17 frozen specimens of neuroblastomas with an anti-GD2 antibody which has the same epitope as the one used in immunotherapy (monoclonal mouse antibody, 14G2A clone). The intensity of staining was graded as follows: “0”, “1+”, “2+”, 3+” and “4+” when 0%, 1-25%, 26-50%, 51-75% and 76-100% of tumor cells respectively showed positive expression. The immunohistochemical results were interpreted without knowledge of the clinical characteristics. Among our patients, 12 have had immunotherapy and 3 of them showed resistance to it.
Results: Immunohistochemical expression of GD2 was found in 96.5% (135/140) of cases, among which 23 had between 1 and 25% of positive tumoral cells. There was a strong correlation between results in frozen and in paraffin sections. Immunostaining intensity was comparable in tumours and in metastasis (1.76 (mean intensity of GD2) vs 1.69) and also when patients were matched up for age (< or > than one year old, 1.82 vs 1.81) and MYCN amplification (2.00 vs 1.63). However, the mean intensity of GD2 expression was significantly higher (2.66 vs 1.33, p-value 0.02) in patients who responded versus those who were resistant to immunotherapy.
Conclusions: The observations of immunohistochemical expression of GD2 in our study show that most neuroblastomas express GD2, but most importantly that there is a significant difference in tumoral expression of GD2 between patients who respond and those who are resistant to immunotherapy. Thus, immunostaining with GD2 could become an important tool in deciding which patients should receive immunotherapy and so avoid overtreatment, but larger studies should be completed beforehand.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 278, Tuesday Afternoon