Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences

Abstract

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.

Mucin Production Correlates with Dual Expression of Epidermal Growth Factor Receptor and Its Ligand the Epidermal Growth Factor in Non-Small Cell Lung Cancer

“…Moreover, it has been reported that upregulated expression of mucins, such as MUC2 and MUC5AC, bind with EGFR and activate the Ras/Raf pathway [38,39]. In line with this, our group previously reported that the dual expression of EGFR and its ligand the EGF is related with increased cell proliferation and with a more aggressive behavior of NSCLC [16].…”

“…Briefl y, the slides were pre-treated with 0.4% pepsin in 0.1N hydrochloric acid solution at 37°C for 30 minutes. Afterward, the tissues were incubated with ior egf/ r3 Mab (anti-EGFR) and CB-EGF1 (anti-EGF ligand) in a humid chamber for 1h at room temperature followed by a rabbit anti- were grouped as follow: low expression (scores < 150) and high expression (scores ≥ 150) as it was previously described in [16] ( …”

Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it’s potential therapeutic implications

“…Our results suggest that it is a frequent phenomenon and thus may support diagnostic considerations. Recently, our colleagues at CIM confirm that the expression of NeuGcGM3 or EGFR alone was associated with poor OS in NSCLC patients [ 9 ]. However, the expression of both targets in the same tumor sample was related with an even poorer prognosis in these patients [ 9 ].…”

“…However, many human tumors express NeuGcGM3 ganglioside [ 2 – 7 ]. The expression of NeuGcGM3 have been associated with a worse prognosis in colon [ 8 ] and lung cancer [ 7 , 9 ]. Differential association between EGFR signaling pathway and GM3 ganglioside expression has been reported [ 10 – 13 ].…”

Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

“…This binding may provoke egFr system activation mediated by the epidermal growth factor ligand (egF). Activation of EGF in the presence of over expressed NeuGcGM3 constitutes a more aggressive immunophenotype in nonsmall cell lung cancer (NsCLC) [10] . Combination of antiegF plus anti-NeugcgM3 immunotherapies are currently under investigation [11] .…”