Comparison of thyroid peroxidase expression with cellular proliferation in thyroid follicular tumors

Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The purpose of this study was to determine the relation of this abnormality with differentiation and proliferative potential of follicular tumors evaluated by analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30 thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our findings confirmed that TPO abnormalities and PCNA index were correlated with malignancy, and that PCNA as well as TPO could be used to determine the growth potential of follicular proliferations in fine-needle aspirates. The most discriminant parameter was the ratio between the percentage of Mab-47 and PCNA positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas. An inverse correlation was found between TPO and PCNA expression, but TG, which persisted at high levels in several actively growing follicular carcinomas, did not appear directly linked to cellular proliferation. These findings confirm that, unlike a decrease in TG synthesis that merely reflects the progressive loss of differentiation occurring in high-grade proliferations, alteration of TPO is an early marker of thyroid follicular tumors, closely related to acceleration of tumor growth in the first stages of malignant transformation.