UDP-N-Acetyl-d-Galactosamine: Polypeptide N-Acetylgalactosaminyltransferase-6 as a New Immunohistochemical Breast Cancer Marker

• Published in: The journal of histochemistry and cytochemistry Vol. 54; no. 3; pp. 317 - 328
• Main Authors: Berois, Nora, Mazal, Daniel, Ubillos, Luis, Trajtenberg, Felipe, Nicolas, André, Sastre-Garau, Xavier, Magdelenat, Henri, Osinaga, Eduardo
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-03-2006
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Biomarkers, Tumor - metabolism; Breast Diseases - enzymology; Breast Neoplasms - enzymology; Breast Neoplasms - 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; N-Acetylgalactosaminyltransferases - metabolism; UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalac-tosaminyltransferases; ppGalNAc-T6; breast cancer; O-glycosylation; immunohistochemistry
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/jhc.5A6783.2005

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.