GalNAcalpha1-3Gal, 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 GalNAcalpha1-3Gal or GalNAcalpha1-6Gal 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 GalNAcalpha1-3Gal with little cross-reactivity to other structurally similar antigens such as GalNAcalpha1-6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. Although GalNAcalpha1-6Gal expression was not detected, GalNAcalpha1-3Gal 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 GalNAcalpha1-3Gal 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.
Li
Qian
Q
Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA.
Anver
Miriam R
MR
Li
Zhitao
Z
Butcher
Donna O
DO
Gildersleeve
Jeffrey C
JC
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism; D002584:Cervix Uteri / Q000737:chemistry / Q000473:pathology; D016009:Chi-Square Distribution; D004187:Disaccharides / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015394:Molecular Structure; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004187:Disaccharides; C086195:N-acetylgalactosaminyl-alpha(1-3)galactose