UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker.

Abstract

Mucin O-glycosylation is characterized in cancer by aberrant expression of immature carbohydrate structures (Tn, T, and sialyl-Tn antigens). The UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-T) family enzymes regulate the initial steps of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. Considering that we recently found the ppGalNAc-T6 mRNA expressed in breast carcinomas, we produced a highly specific monoclonal antibody (MAb T6.3) to assess the expression profile of ppGalNAc-T6 protein product in breast tissues. The expression of ppGalNAc-T6 by breast carcinoma cells was confirmed on MCF-7 and T47D cell lines. In formalin-fixed tissues, ppGalNAc-T6 expression was observed in 60/74 (81%) breast cancers, 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), 4/20 benign breast lesions (2/2 sclerosing adenosis and 2/13 fibroadenoma), and in 0/5 normal breast samples. We observed a statistically significant association of ppGalNAc-T6 expression with T1 tumor stage. This fact, as well as the observation that ppGalNAc-T6 was strongly expressed in sclerosing adenosis and in most DCIS, suggests that ppGalNAc-T6 expression could be an early event during human breast carcinogenesis. Considering that an abnormal O-glycosylation greatly contributes to the phenotype and biology of breast cancer cells, ppGalNAc-T6 expression could provide new insights about breast cancer glycobiology.

• Authors: Nora Berois, Daniel Mazal, Luis Ubillos, Felipe Trajtenberg, André Nicolas, Xavier Sastre-Garau, Henri Magdelenat, Eduardo Osinaga
• Journal: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (J Histochem Cytochem) Vol. 54 Issue 3 Pg. 317-28 (Mar 2006) ISSN: 0022-1554 [Print] United States
• PMID: 16260590 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Biomarkers, Tumor
• N-Acetylgalactosaminyltransferases
• UDP-N-acetylgalactosamine polypeptide N-acetylgalactosaminyltransferase 6

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antibodies, Monoclonal
• Biomarkers, Tumor (metabolism)
• Breast Diseases (enzymology)
• Breast Neoplasms (enzymology, pathology)
• Carcinoma, Ductal, Breast (enzymology)
• Carcinoma, Lobular (enzymology)
• Carcinoma, Papillary (enzymology)
• Female
• Humans
• Immunohistochemistry
• Mammary Glands, Human (enzymology)
• Metaplasia
• Mice
• Middle Aged
• N-Acetylgalactosaminyltransferases (immunology, metabolism)