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JHC exPRESS: First Published October 31, 2005. doi:10.1369/jhc.5A6783.2005
Copyright © Histochemical Society, Inc.

A more recent version of this article appeared on March 1, 2006.
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UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a New Immunohistochemical Breast Cancer Marker

Nora Berois 1, Daniel Mazal 1, Luis Ubillos 1, Felipe Trajtenberg 1, André Nicolas 1, Xavier Sastre-Garau 1, Henri Magdelenat 1 and Eduardo Osinaga 1*

1 Departamento de Bioquímica, Laboratorio de Oncología Básica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay (NB,DM,LU,FT,EO), and Département de Biologie des Tumeurs, Institut Curie, Paris, France (AN,XS-G,HM)

* To whom correspondence should be addressed. E-mail: eosinaga{at}fmed.edu.uy.

Submitted on July 16, 2005
Accepted on 11 October 2005


  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, in 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), in 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.

Key Words: breast cancer, immunohistochemistry, O-glycosylation, UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases, ppGalNAc-T6


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[Abstract] [Full Text] [PDF]



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