POSSIBLE RELATION OF P53 AND MDM-2 ONCOPROTEIN EXPRESSION IN THYROID-CARCINOMA - A MOLECULAR-PATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY ON PARAFFIN-EMBEDDED TISSUE

Routinely processed tissues from a series of benign and malignant thyr oid lesions were immunohistochemically investigated with antibodies ag ainst p53 and mdm-2. p53 was immunolocalized in <10% of nuclei in 2/80 nodular goiters, 2/60 follicular adenomas, 26/68 follicular carcinoma s, 7/40 papillary carcinomas, 3/10 ''insular'' carcinomas, and 10/31 a naplastic carcinomas. More than 10% positively stained nuclei were fou nd in 2 widely invasive follicular, 2 insular, and 15 anaplastic carci nomas. All p53-positive cases showed a concomitant immunohistochemical mdm-2 expression; an immunohistochemical colocalization on serial sec tion was demonstrated in 12 anaplastic carcinomas. Screening by polyme rase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis of these 12 cases revealed no relevant mutations in the codi ng regions of exons 2-11 of the p53 gene. Additionally, 1 follicular a denoma, 6 follicular carcinomas (4 minimally and 2 widely invasive), 1 papillary, and 2 poorly differentiated insular carcinomas were mdm-2 positive without immunohistochemically detectable p53 expression. Thes e results provide evidence that wild-type p53 expression in thyroid ca rcinomas may be associated with mdm-2 induced formation of stable comp lexes. However, the role of p53 mutations and p53 protein inactivation owing to other factors (e.g., mdm-2) in the progression of thyroid ca rcinomas is still poorly understood.