GalNAc alpha 1-3Gal, a new prognostic marker for cervical cancer

Cancer cells undergo significant changes in carbohydrate expression, and these alterations can be useful as biomarkers and therapeutic targets. In this study, we investigated the expression of carbohydrate antigens containing a terminal GalNac alpha-1-3Gal or GalNAc alpha 1-6Gal on human cervix and cervical carcinoma. Monoclonal antibodies to each of these carbohydrates were generated by immunizing rabbits with the corresponding antigen conjugated to KLH followed by hybridoma production. Antibodies were screened and evaluated using a combination of carbohydrate microarray profiting, ELISA, dot blot and immunohistochemical staining to verify specificity. Antibody 132-3 was found to selectively recognize GalNAc alpha 1-3Gal with little cross-reactivity to other structurally similar antigens such as GalNAc alpha 1-6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. Although GalNac alpha 1-6Gal expression was not detected, GalNac alpha 1-6Gal expression was found on 55% of squamous cell carcinomas. Expression in normal tissue was observed but was restricted to the suprabasal epithelial layer. Importantly, we found expression of the antigen on cervical cancer had a statistically significant correlation with the 5-year survival rate of the patients (48 vs. 85% for antigen negative vs. positive, p = 0.017). Expression of GalNAc alpha 1-3Gal did not correlate with other clinical factors including tumor stage, size and lymph node metastasis, indicating the antigen is a new, independent biomarker for the prognosis of cervical cancer. Published 2009 UICC. This article is a US Government work and, as such, is in the public domain in the United States of America.

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