Papillary thyroid cancer is the most common endocrine
malignancy. Of all solid
cancers presenting in adults,
papillary thyroid cancer generally carries the best long-term prognosis. However, very little is understood about the molecular pathogenesis of this
neoplasm. We recently hypothesized that increased nuclear levels of
MDM2 protein might occur in well-differentiated
papillary thyroid carcinomas (Gerasimov et al., Exp. Mol. Pathol. 62, 52-62, 1995). MDM2 is known to complex with and inactive the
p53 tumor suppressor protein. Since p53 inactivation by gene mutation has an established role in the pathogenesis of undifferentiated (
anaplastic) thyroid carcinoma, we reasoned that abrogation of p53 function by nuclear
MDM2 protein accumulation might participate in the pathogenesis of certain well-differentiated
thyroid cancers such as papillary
cancer. In the present report we present the first direct evidence of
MDM2 protein accumulation in the nuclei of
papillary thyroid carcinoma cells in a subset of
tumors. Using the IF-2
monoclonal antibody, which reacts specifically with
human MDM2 protein, we studied 24 well-differentiated
papillary thyroid carcinomas and 26 benign lesions (
nodular goiters,
adenomas,
thyroiditis). Nuclear staining was quantitated using the CAS computerized image analysis system. We found positive nuclear MDM2 immunoreactivity in 8 (33%) of the
carcinomas. In contrast, MDM2 staining was negative in all benign lesions (P = 0.001, two-tailed Fisher exact test). Normal thyroid tissue was also negative. These data suggest that nuclear accumulation of
MDM2 protein might be implicated in the pathogenesis of a subset of
papillary carcinomas. Further studies to investigate this possibility are warranted.