NUCLEAR P53 IMMUNOREACTIVITY IN PAPILLARY THYROID CANCERS IS ASSOCIATED WITH 2 ESTABLISHED INDICATORS OF POOR-PROGNOSIS

The tumor suppressor protein, p53, protects somatic cells against the accumulation of genomic alterations. Cells harboring mutant or inactiv ated wild-type p53 protein are at risk for the development of genomic instability. Nuclear accumulation of p53 protein is associated with th e stepwise dedifferentiation of papillary carcinoma. We asked whether nuclear p53 accumulation is associated with two known indicators of po or prognosis in papillary carcinoma. We studied 55 consecutive papilla ry cancers (28 from Russia, and 27 from upstate New York). Nuclear p53 immunoreactivity was assessed using a monoclonal antibody, DO-1, on F ormalin-fixed paraffin-embedded specimens. The DNA index was determine d by computerized image analysis of Feulgen-stained sections. Nearly a ll cases were well differentiated and none were associated with distan t metastases or extrathyroidal invasion. All primary lesions were less than 4 cm in diameter, and almost all patients were female. Nuclear p 53 immunoreactivity was associated with a high-risk group characterize d by two known indicators of poor prognosis: age >50, aneuploid DNA co ntent, or both. In the high-risk group (N = 24) 33% of cases displayed nuclear p53 positivity, compared with only 6% in a low-risk group (N = 31) which lacked bath features (P = 0.015, two-tailed Fisher exact t est). Nuclear accumulation of immunoreactive p53 protein is associated with two established indicators of poor prognosis in papillary carcin oma of the thyroid. This result is consistent with the idea that aberr ations in p53 function are associated with the stepwise loss of differ entiation in this cancer. (C) 1995 Academic Press, Inc.