The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior.

Abstract

Hypoxic areas in solid tumors are often associated with poor prognosis and resistance to chemotherapy. The aim of the study was to analyze the expression of galectin-1 (Gal-1), galectin-3 (Gal-3), sialic acid and b1-6 branched glycan structures in hypoxic environment of invasive ductal carcinoma (IDC) of the breast. We performed lectin histochemistry with phytohemag glutinin-L (L-PHA) and Sambucus nigra lectin (SNA); and immunohistochemistry for Gal-1, Gal-3, carbonic anhydrase IX, hypoxia-inducible factor, estrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor type-2 for 86 IDC samples. Patients with markers positive for hypoxia were mostly ER-negative (p = 0.003) and presented with more nodal invasion than the non-hypoxic group (p = 0.0439). Concerning the glycobiological aspects, the hypoxic group expressed more of Gal-3 (p = 0.0021) and SNA ligands (p = 0.0498), however, there was no association between lectin- and galectin-staining and clinical and histopathological data. Our results suggest a change in the glycomic profile of patients within hypoxic regions of IDC. However, further studies are needed to evaluate the role of lectin- and galectin-ligands in tumor's hypoxic environment, as well as their potential to be used as therapeutic targets.