The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended.
Several biosimilars for Herceptin® (trastuzumab) and other innovator monoclonal antibodies (mAbs) against HER2 molecule have been developed and approved in the last years. Here, it is reported the binding properties of a novel anti-HER2 mAb (called 5G4) as well as the capacity of this mAb to inhibit cell proliferation and to induce Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). mAb 5G4 was compared with Herceptin® in a panel of human normal tissues, breast tumors and cell lines using immunohistochemistry, immunocytochemistry, western blot, flow cytometry and colorimetric methods. mAb 5G4 showed weak to moderate staining in breast ductal cells (1/2), gastric glandular cells (1/3) and renal tubes (2/3). Additionally, an intense reactivity was evident with mAb 5G4 in HER2-positive breast adenocarcinomas. The tissue staining was slightly more intense with Herceptin® (trastuzumab) that was used as control. Flow cytometry analysis revealed that mAb 5G4 is able to react with HER2 overexpressing cells (SK-BR-3 and SKOV3) comparable to Herceptin®. The relative binding and the anti-proliferative activity ranges of mAb 5G4 using Herceptin® as reference were between 91-115% and between 91-106%, respectively, which are considered comparable. Moreover, preliminary results suggest that the capacity of mAb 5G4 to induce ADCC in SK-BR-3 cells is non-inferior to Herceptin®. Our data permit to consider that mAb 5G4 has similar binding properties to HER2 antigen and biological activity compared with Herceptin®. However, further determinations such as affinity and FcgRIIIa binding activity of mAb 5G4 could be useful to confirm these results.
Introduction: Mucoproduction plays an important role in the processes of tumor progression, invasion and metastasis. In non-small cell lung cancer (NSCLC), mucins hypersecretion has been associated with alterations in the epidermal growth factor receptor (EGFR) expression. However, the relation of mucins with EGFR in these tumors is not completely clarifi ed.
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