Anti-Tn and Anti-Sialyl-Tn Antibodies in the Evaluation of Thyroid Neoplasms and Normal Thyroid Tissue
Harold C Sullivan, Sean R Stowell, Richard D Cummings, Brian C Quigley, Momin T Siddiqui, Cynthia Cohen. Emory University, Atlanta, GA
Background: Investigators have long attempted to identify cancer-associated antigens. Consequently, antibodies have been created to aid in diagnosis. Recent studies suggest that alterations in post-translational modifications to Tn and sialyl-Tn (sTn) carbohydrates may occur following mutations in Cosmc, a key regulator of these modifications. These aberrant modifications could serve as unique targets of neoplastic disease. Tn, normally immunologically inaccessible in adult human tissue, has been shown to be expressed in endometrial, breast, ovarian, lung, colon, pancreatic, and urothelial carcinomas. The purpose of this study is to determine Tn and sTn expression in neoplastic and nonneoplastic thyroid tissue, in which determination of neoplastic vs. nonneoplastic is challenging, especially in cytology and surgical specimens where the differential includes follicular adenoma and carcinoma.
Design: Tissue microarrays (TMAs) of thyroid neoplasms and adjacent normal thyroid were created. Neoplasms included papillary thyroid carcinoma, follicular carcinoma, follicular adenoma, anaplastic carcinoma, medullary carcinoma, Hurthle cell neoplasms, and multinodular goiters. TMAs were immunostained with Tn and sTn monoclonal antibodies identified by glycan microarray at Emory University. Expression for both antigens was cytoplasmic. An immunostain intensity of 2 (scale:0-3) and a percentage of positive-staining cells of >5% were considered positive.
Results: See table.
|Tissue type (no.)||Tn positive no. (%)||P-value*||sTn Positive no. (%)||P-value*|
|Normal (140)||0 (0)||N/A||0 (0)||N/A|
|Papillary thyroid carcinoma (94)||3 (3)||0.64||0 (0)||N/A|
|Follicular carcinoma (52)||0 (0)||N/A||0 (0)||N/A|
|Follicular adenoma (8)||0 (0)||N/A||0 (0)||N/A|
|Anaplastic carcinoma (14)||4 (29)||<0.0001||0 (0)||N/A|
|Medullary carcinoma (2)||0 (0)||N/A||0 (0)||N/A|
|Hurthle cell neoplasm (25)||0 (0)||N/A||1 (4)||0.151|
|Multinodular goiter (38)||0 (0)||N/A||1 (3)||0.212|