ALTERATIONS OF P53 AND EXPRESSION OF WAF1 P21 IN HUMAN THYROID-TUMORS/

We have investigated p53 expression in 178 thyroid tumors from 162 pat ients by immunohistochemistry using two antibodies, DO1 and CM1. in ad dition, 35 tumors were analyzed for expression of WAE1/p21, one of the downstream mediators of p53. Only 15 tumors (8.4%) had greater than 1 0% of tumor cell nuclei positively stained for p53. Six of 14 Hurthle tumors and three of 34 papillary thyroid carcinomas showed staining of p53 in the cytoplasm. A total of 40 tumors, including all p53 positiv e tumors, and all anaplastic and poorly differentiated tumors were scr eened for mutations in exons 5-8 of the TP53 gene by constant denaturi ng gel electrophoresis and subsequent sequence analysis. A mutation wa s detected in five tumors only: one anaplastic carcinoma, one poorly d ifferentiated follicular carcinoma (negative by p53 immunohistochemist ry), one atypical follicular adenoma, and two papillary thyroid carcin oma metastases, of which the primary tumors had no detectable mutation . We conclude that p53 immunohistochemistry cannot be used for diagnos tic and prognostic purposes in thyroid tumors. The tumors with TP53 mu tation showed a markedly reduced WAF1/p21 expression. Three anaplastic carcinomas with highly expressed p53, but with no detectable mutation , also showed high expression of WAF1/p21. This may be explained by ov erexpression of wild-type p53, possibly due to the patients' preoperat ive treatment, including external radiation of the neck region. The re sults indicate that WAF1/p21 immunohistochemistry contributes to the i nformation of the functional status of p53, and may facilitate the int erpretation of results from p53 immunohistochemistry in these tumors.