Helix pomatia Agglutinin Binding Glycoproteins in Thyroid Tumors

Abstract

Binding of the lectin Helix pomatia agglutinin (HPA) has been shown to be associated with poor prognosis in many human cancers, but not in thyroid cancer. The aims of the present study were to assess alteration in cellular glycosylation, detected by HPA binding, in thyroid tumors; to determine if such altered glycosylation carries any prognostic significance; and to analyze qualitative and quantitative differences of HPA-binding glycoproteins in various thyroid tumors. Lectin histochemistry was performed on 110 archival paraffin wax embedded specimens of various thyroid tumors excised between the years 1983-1993. Demographic data, histological data, and time to death were recorded, and multivariate Cox regression analysis was performed to determine a prognostic model for patient survival based on the data. Helix pomatia agglutinin binding glycoproteins were isolated from 128 fresh specimens of various thyroid tissues by affinity chromatography, analyzed by SDS-PAGE and western blotting. There was a marked qualitative difference in the profile of HPA-binding glycoproteins, with the malignant thyroid tumors showing a heterogeneous profile of numerous HPA binding glycoprotein bands. Lectin histochemistry showed significant positive HPA binding in malignant thyroid tumors (p = 0.0009). Kaplan-Meir survival analysis revealed that among patients who died of their disease those with HPA-positive tumors had a significantly shorter survival (p = 0.009). This is the first study showing that HPA binding glycoproteins are synthesized by thyroid tumors. Thyroid cancers show a broader profile of HPA binding glycoproteins compared to benign thyroid tumors, and positive HPA binding is significantly associated with shorter survival and poorer prognosis in thyroid cancers.