GD2 expression in breast cancer

Abstract

Breast cancer (BC) is a heterogeneous disease, including different subtypes having diverse incidence, drug-sensitivity and survival rates. In particular, claudin-low and basal-like BC have mesenchymal features with a dismal prognosis. Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a variety of cancers. Despite its potential relevance in cancer diagnostics and therapeutics, the presence and role of GD2 require further investigation, especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC patients and its correlation with clinical-pathological features.Sixty-three patients with BC who underwent surgery without prior chemo- and/or radiotherapy between 2001 and 2014 were considered. Cancer specimens were analyzed by immunohistochemistry and GD2-staining was expressed according to the percentage of positive cells and by a semi-quantitative scoring system.Patient characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in 59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11 (18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens stained positive for GD2. The univariate regression logistic analysis revealed a significant association of GD2 with triple-receptor negative phenotype and older age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly prevalent in a cohort of BC patients clustering on very aggressive BC subtypes, such as triple-negative and metaplastic variants.

GD2-targeted chimeric antigen receptor T cells prevent metastasis formation by elimination of breast cancer stem-like cells

“…They found GD2 expression in 59% of samples with increased prevalence toward highly aggressive breast cancer subtypes, such as TNBC and metaplastic variants. 20 In our study, we analyzed GD2 expression on a small panel of breast cancer cell lines. In line with Batulla et al, we found GD2 expression in a subpopulation of cells, possibly BCSCs, in the cell lines T-47D (luminal A) and MDA-MB-231 (TNBC basal B).…”

“…17,18 GD2 expression on breast cancer and BCSC was independently verified by different groups. 19,20 Notably, GD2 is an excellent and extensively studied target antigen for antibody-based immunotherapy. 21 We and others have clinically evaluated GD2 mAbs to treat patients suffering from metastatic neuroblastoma, leading to significantly improved survival and FDA/EMA approval of ch14.18, also known as dinutuximab beta.…”

Don’t sugarcoat it: How glycocalyx composition influences cancer progression

“…Furthermore, the GD3 structure has been shown to bind and suppress both T helper and NKT cell function in brain and ovarian cancers (Mycko et al, 2014; Webb et al, 2012). GD2 is also a well-known ganglioside that is up-regulated in in melanoma, lung cancers, sarcomas, neuroblastomas, and triple-negative breast cancers (Dobrenkov et al, 2016; Orsi et al, 2017; Terzic et al, 2018; Yanagisawa et al, 2011). GD2 associates with the VLA-2 integrin and up-regulates the binding of neuroblastomas to ECM proteins such as collagens.…”

Ganglioside GD3 synthase (GD3S), a novel cancer drug target

“…In particular, GD2 is highly expressed in melanomas and small cell lung cancer cells, and its expression promotes growth and invasion of cells 41 . GD2 is also highly prevalent in a cohort of breast cancer (BC) patients clustering on very aggressive breast cancer subtypes, such as triple-negative and metaplastic variants 52 . What׳s more, GD2 is highly expressed in sarcomas of children, adolescents and young adults 53 and the majority of human osteosarcoma cell lines derived from oral cavity regions 54 .…”