The Phenotype of Hurthle and Warthin-like Papillary Thyroid Carcinomas Is Distinct From Classic Papillary Carcinoma as to the Expression of Retinoblastoma Protein and E2F-1 Transcription Factor

Abstract

Retinoblastoma protein plays an important role in controlling cell cycle progression. The active form of retinoblastoma protein binds to E2F-1 and inhibits transcription of S phase genes. Overexpression of E2F-1 has been suggested as an important factor in carcinogenesis. The Hurthle cell (HPCA) and Warthin-like (WLPCA) variants of papillary carcinoma are two closely related entities that arise in association with Hashimoto's thyroiditis and share the presence of oxyphilic changes in the lining of epithelial cells and the presence of papillary nuclear features. The current study included formalin-fixed, paraffin-embedded tissues from 58 cases of thyroid papillary carcinoma: 20 HPCA, 6 WLPCA, 22 conventional papillary carcinomas (PCA), and 10 follicular variants of papillary carcinoma (FVPCA). The immunohistochemical studies were performed for retinoblastoma (Rb-1) and E2F-1, (KH95) after heat-induced epitope retrieval. None of the PCA or FVPCA cases were in the positive range for Rb-1. All cases of HPCA and WLPCA of the thyroid showed reactivity in 50% or more of the nuclei in the neoplastic cell population. As for E2F-1, all cases of HPCA and WLPCA showed positive reactivity, whereas none of the PCA or FVPCA cases were in the positive range. In conclusion, HPCA and WLPCA are Rb-positive and E2F-1-positive; PCA and FVPCA are Rb-negative and E2F1-negative. Hurthle metaplastic epithelium in Hashimoto's thyroiditis is Rb-positive and E2F-1-negative. This phenotypic difference is also helpful in distinguishing hyperplastic Hurthle cell proliferation in Hashimoto's thyroiditis from HPCA or WLPCA.