Anti-Tn Antibody Specifically Recognizes Neoplastic Lesions
Sean R Stowell, Casey Gooden, Cynthia Cohen, Tongzhong Ju, Richard D Cummings. Emory University, Atlanta, GA
Background: Since the earliest description of neoplastic disease, investigators sought to identify unique features of transformed tissue to provide more accurate diagnosis and treatment. However, many potential targets display expression in a limited subset of disease or simply represent dysregulation of pathways present in many types of non-transformed tissue. Several recent studies suggest that a specific post-translational modification, the carbohydrate Tn antigen, may occur following mutations in a key regulator of post-translational modifications, Cosmc. However, lack of well-defined reagents previously limited a thorough examination of Tn antigen expression in normal and neoplastic tissue. As a result, we characterized an anti-Tn antibody and examined the expression of the Tn antigen in normal and transformed tissue.
Design: The specificity of a mouse IgM anti-Tn antibody was evaluated using the Consortium for Functional Glycomics glycan microarray and a series of cell lines with mutated or wt Cosmc using flow cytometric analysis and immunohistochemistry. To determine level and specificity of anti-Tn antibody reactivity within neoplastic lesions, paraffin blocks were selected from normal tissue and cases broadly classified as breast (39), ovarian (43), endometrial (41), colon (51), and lung (48) cancer followed by examination for anti-Tn reactivity by semiquantitative immunohistochemistry (negative, 1+, 2+ and 3+). Comparative reactivity of anti-Tn between neoplastic and normal tissue was assessed using the student T test.
Results: The anti-Tn antibody displayed significant and specific reactivity toward the Tn antigen following analysis of several hundred structurally diverse post-translational modifications. Consistent with this, the anti-Tn antibody only recognized cell lines harboring mutations in Cosmc. Importantly, while the anti-Tn antibody failed to exhibit >1+ reactivity toward any of the non neoplastic tissue examined, it displayed >1+ reactivity in 74% of ovarian, 67% of colon, 56% of breast, 55% of endometrial and 53% of lung cancer lesions (p<0.05).
Conclusions: Taken together, these results strongly suggest that anti-Tn antibody specifically recognizes Tn expressing cells and that Tn antigen expression uniquely occurs following neoplastic transformation. These results implicate Cosmc as a key player in neoplastic pathogenesis and strongly suggest that the Tn antigen may serve as a versatile diagnostic tool and therapeutic target.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 283, Monday Morning