N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.

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

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.

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study.

BACKGROUND: The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, ß1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of ß1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of ß1 integrin in patients with ductal carcinoma in situ (DCIS). METHODS: Through tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, ß1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance. RESULTS: ß1 integrin was overexpressed in 32.8% of IDC. In IDC, ß1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding ß1 integrin expression. CONCLUSIONS: Considering that the expression of ß1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that ß1 integrin can be a marker of poor prognosis in breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871.