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GalNAcα1‐3Gal, a new prognostic marker for cervical cancer
Author(s) -
Li Qian,
Anver Miriam R.,
Li Zhitao,
Butcher Donna O.,
Gildersleeve Jeffrey C.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24716
Subject(s) - antigen , immunohistochemistry , monoclonal antibody , cervical cancer , antibody , cancer , western blot , pathology , metastasis , biology , medicine , cancer research , immunology , gene , biochemistry
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 GalNAcα1‐3Gal or GalNAcα1‐6Gal 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 profiling, ELISA, dot blot and immunohistochemical staining to verify specificity. Antibody 132‐3 was found to selectively recognize GalNAcα1‐3Gal with little cross‐reactivity to other structurally similar antigens such as GalNAcα1‐6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. Although GalNAcα1‐6Gal expression was not detected, GalNAcα1‐3Gal 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 GalNAcα1‐3Gal 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.